1-phenylsulfonyl-2-imino-imidazolidines and hexahydropyrimidines



United States Patent 3,538,085 l-PHENYLSULFONYL-Z-IMINO-IMIDAZOLIDINESAND HEXAHYDROPYRIMIDINES Henri Dietrich, Arlesheim, Switzerland,assignor to Geigy Chemical Corporation, Ardsley, N .Y., a corporation ofNew York No Drawing. Continuation-impart of application Ser. No.624,195, Mar. 20, 1967. This application Oct. 23, 1968, Ser. No. 770,102

Claims priority, application Switzerland, Mar. 24, 1966,

' 4,280/66; Mar. 14, 1968, 3,881/68, 3,882/68 Int. Cl. A61k 27/00; C07d49/34, 51/42 U.S. Cl. 260-2393 Claims ABSTRACT OF THE DISCLOSURE Vl-phenylsulfonyl 2-imino imidazolidines and -hexahydropyrimidines,substituted at the heterocyclic ring and substituted or unsubstituted atthe phenyl ring are prepared; these compounds and their pharmaceuticallyacceptable acid addition salts have hypoglycemic activity;pharmaceutical compositions comprising said compounds and methods ofproducing hypoglycemic effects in mammals are provided; an illustrativeembodiment is l-sulfanilyl-2-imino-3-butyl-imidazolidine.

CROSS REFERENCE TO RELATED APPLICATIONS This is a continuation-in-partapplication of copending patent application Ser. No. 624,195, filed Mar.20, 1967, now abandoned.

DETAILED DISCLOSURE This invention relates to hypoglycemically active 1-phenylsulfonyl 2-imino-imidazolidines andl-phenylsulf0nyl-2-iminohexahydropyrimidines pharmaceutically acceptableacid addition salts thereof, their production, pharmaceuticalcompositions containing them and a method of producing a hypoglycemiceffect comprising administration of such compounds.

More particular the invention relates to phenylsulfonamide derivativesof the Formula I and pharmaceutically acceptable acid addition saltsthereof, which compounds on oral or parenteral administrat on havestrong hypoglycemic activity. This fact is surprising, because it isknown in the art that sulfanilylguanidines and N-alkyl derivativesthereof of the formula wherein R is hydrogen or alkyl, andN-(l-imidazolin-Z- yl)-p-chlorophenylsulfonamide of the formula have nohypoglycemic activity.

The hypoglycemic activity of the compounds of the invention isfurthermore surprising, because p-substituted 1phenylsulfonyl-2-irnidazolidinones, e.g. of the formula R' SOHL in,

have hyperglycemic activity, i.e. they increase theblood sugar level inmammanls.

Moreover, in contrast to sulfanilylguanidines and N- sulfanilyl-N-alkylureas, the compounds according to the invention are free fromantibacterial activity.

These beneficial properties in combination with a. favourabletherapeutic index render the compounds of the invention well suited forthe treatment of diabetes.

In the compounds of Formula I, R R R R R and X as lower alkyl groups canbe an alkyl group of from 1 to 4 carbon atoms, eg the methyl, ethyl,propyl, iso-propyl, butyl, i-butyl, sec. butyl or tert. butyl group.Furthermore R can be, e.g. the following groups; as alkyl group an alkylgroup of from 5 to 12 carbon atoms, e.g. the pentyl, i-pentyl,2,2-dimethylpropyl, l-methylbutyl, l ethylpropyl, 1,2 dimethylpropyl,hexyl, heptyl, octyl, nonyl, decyl or dodecyl group; as alkenyl group analkenyl group of from 3 to 4 carbon atoms, e.g. the allyl, 1methylallyl, 2 r nethylallyl or the 2 butenyl group; as alkoxyalkyl oralkylthioakyl an alkyl group of from 3 to 8 carbon atoms which isinterrupted by an oxygen ether or a thioether bond, e.g. the2-methoxyethyl, 3- methoxypropyl, 4 methoxybutyl, 2 ethoxyethyl, 3ethoxypropyl, 4 ethoxybutyl, 2 propoxyethyl, 3 pro poxypropyl, 4propoxybutyl, 2 i propoxyethyl, 3-ipropoxyethyl, 4 i propoxybutyl, 2butoxyethyl, 3- butoxypropyl or the 4-butoxybutyl group as well as thecorresponding thioether; as cycloalkyl group a saturated cyclichydrocarbon group of from 3 to 10 carbon atoms, which can be substitutedwith a methyl or an ethyl group, e.g. the cyclopropyl,methylcyclopropyl, cyclobutyl, methylcyclobutyl, cyclopentyl,methylcyclopentyl, cyclohexyl, methylcyclohexyl, ethylcyclohexyl,cycloheptyl, methylcycloheptyl, cyclooctyl, methylcyclooctyl,cyclononyl, cyclodecyl, adamantyl or the norbornyl group; ascycloalkenyl group an unsaturated cyclic hydrocarbon group of from 5 to9 carbon atoms with one double bond, eg the 2 cyclopenten 1 yl,2-cyclohexen-l-yl, 3-cyclohexenl yl, 2 methyl 2-cyclohexen-l-yl,3-met-hyl-2-cyclohexen 1 yl, 3 methyl-5-i-propyl-2-cyclohexen-1-y1 orthe 4 cycloocten 1 yl group, and as aralkyl group preferably aphenylalkyl group, e.g. the benzyl or the phenethyl group.

. A preferred class of compounds of particular strong hypoglycemicactivity and freedom from antibacterial activity are compounds ofFormula Ia wherein each of R' and R',, independently of the other, ishydrogen or lower alkyl, R' is alkyl and cycloalkyl having at mostcarbon atoms, and X is amino, chloro, methoxyand acetyl, and thepharmaceutically"acceptable acid addition salts thereof.

Accordingto a first process the compounds of Formula I are produced byreacting, optionally in the presence of an acid binding agent, areactive functional derivative of a sulfonic acid of the formula whereinX has the meaning as defined for X under Formula I, except amino, andhas the meaning of a masked amino group convertible into an amino groupby hydrolysis, reduction or reductive cleavage, with a compound of theformula wherein n, R R R R and R have the meanings given in Formula I,where applicable hydrolysing or reducing the reaction product obtainedto convert the group X into the free amino group and, if desired,converting the compound obtained into an acid addition salt.

' A-s reactive functional derivatives of Formula II are suitable thehalides, particularly the chlorides, and the anhydrides of the formulaThe reaction is preferably performed in the presence of a water miscibleor water non-miscible inert organic solvent in the presence or absenceof water. Suitable inert organic solvents are, e.g., hydrocarbons suchas benzene, toluene or xylene, ether-type solvents such as diethylether, dioxane or tetrahydrofuran, chlorinated hydrocarbons such asmethylene chloride, and lower ketones such as acetone or methyl ethylketone. Inorganic bases or salts can be used as acid binding agents,e.-g., an alkali hydroxide, acetate, hydrogen carbonate, carbonate andphosphate such as sodium hydroxide, sodium acetate, sodium hydrogencarbonate, sodium carbonate and sodium phosphate, or the correspondingpotassium compounds. In addition, calcium oxide, calcium carbonate,calcium phosphate and magnesium carbonate can be used. Also organicbases such as pyridine, trimethylamine or triethylamine,N,N-di-isopropylmethylamine or collidine are suitable. Used in excess,these can also serve as solvents.

' A masked amino group X" of the reaction product is subsequentlymodified by hydrolysis, reduction or reductive cleavage depending on thetype of the group X into the free amino group to convert this productinto a compound of Formula I.

Examples of masked amino groups X" which can be converted by hydrolysisinto the free amino group are acylamino groups such as the acetamidogroup; also lower alkoxycarbonylamino groups such as theethoxycarbonylamino group; aryloxycarbonylamino groups such as thephenoxycarbonylamino group; or arylmethoxycarbonylamino groups such asthe benzyloxycarbonylamino groups; or groups of correspondingthiocarbonic acid derivatives. Further examples are substitutedmethyleneamino groups such as the benzylideneamino orp-dimethylamino-benzylideneamino group..

The hydrolysis to liberate the amino group can be performed, e.g.- in.an acidmedium such as-by heating in dilute methanolic hydrochloric acidor, if X" is an alkoxycarbonylamino group, it can also be performedunder mildalkaline conditions, e.g. with '1 N-to 2 -N sodium hydroxidesolution.

An example for a group X" which can be converted into the amino group byreduction is the nitro group and examples of those groups which leadtothe amino group by reductive cleavage are the phenylazo orp-dimethylamino-phenylazo groups. In general, these radicals can bereduced catalytically, e.g. by means of hydrogen in the presence ofRaney nickel, palladium or platinum charcoal, in an inert solvent such'as ethanol. Other usual reduction processes apart from these can beused, for example, the reduction of nitro groups or the reductivecleavage of azo groups by means of iron in acetic or hydrochloric acid.

. Examples of starting materials of Formula III respectively IIIawherein n is 0 are 1-methyl-, 1-ethyl-, l-propyl-, l-isopropyl-,1-butyl-, 1-isobutyl-, l-sec. butyl-, l-tert. butyl-, 1-pentyl-,1-isopentyl-, 1-(l,l-dimethyl-propyl)-, l-cyclopropyl-,1-cyclopropylmethy1-, 1-cyclobutyl-, l-cyclobutylmethyl-,1-cyclopentyl-, 1-cyclopenty1methyl-, 1- cyclohexyl,1-cyclohexylmet'hyl-, 1-(2-cyclohexylethyl)-, l-cycloheptyl,l-cycloheptylmethyl, l-cyclo-octyland lcyclo-octylmethyl-,l-cyclononyl-, l-cyclodecyl-, 2-cyclopenten-l-yl-, 2-cyclohexen-l-yl-,3-cyclohexen-l-yl-, 2- methyl-Z-cyclohexen-l-yl-,3-methyl-2-cyclohexen-1-yl-, 3- methyl-S-isopropyl-2-cyclohexen-l-yland4-cyclo-octen-lyl-2-amino-2-imidazoline.

l-methyl-, l-cyclohexyland 1-(2-cyclohexylethyl)-2- aminoimidazolinehave been describedin the literature.

Other compounds are obtained analogously, e.g. by starting fromethylenediamines substituted corresponding to the definition of R TheseN-substituted ethylenediamines are reacted, e.g. with carbon disulfideto form 1- substituted Z-imidazolidine thiones. These are converted withmethyl iodide into correspondingly substituted 2-methylthio-2-imidazolinium iodides which, on reaction with ammonia,yield the desired compounds of Formula III respectively IIIa. Thesecompounds are obtained by another process by condensation ofN-substituted ethylenediamines with cyanogen chloride or bromide. Athird process consists in reacting an N-substituted ethylenediamine witha salt of S-methyl-isothiourea to form the corresponding salt of anN-(Z-substituted aminoethyl)- guanide and heating this until the ring isclosed to form the corresponding salt of a l-substituted2-amino-imidazoline. In analogy to the production of the knownhomologous l-dodecyl-2-amino-imidazoline, a fourth process is thereaction of the Z-imino-imidazolidine with a lower amine to form2-chloro-N-benzyl-propionamide, which is reacted with *an'amine NH R tothe corresponding 2-R -amino-N-benzyl-propionamide. The latter isreduced with lithium aluminium hydride in tetrahydrofuran to give1-benzylamino-2-R -amino-propane, which in turn is debenzylated withhydrogen and palladium to give 1- amino-2-R -amino-propane. This diamineis finally reacted with cyanogen bromide to form 1-R-2-amino-5-rnethylimidazoline. Similarly 2-amino-imidazolinessubstituted at N and in 4- and S-position are prepared analogously.

Starting materials of Formula III, "respectively IIIa, wherein n is l,i.e. substituted Z-imino-hexahydropyrimidines, are also known in theliterature or can be prepared 5 in analogy to processes for thepreparation of the imidazolines described hereinbefore.

Compounds of Formula I can be prepared according to a second process bycondensing and cyclising a compound of the formula R4 (CHM R3 Rr -R2 XLIOHI M,

I l fl (IV) wherein n, R R R R and R have the meanings as defined underFormula I and X" has the meaning as defined under Formula II, with areactive functional derivative of cyanic acid, if necessary hydrolysingor reducing the reaction product obtained to transform the group X" intoa free amino group and, if desired, converting the compound obtainedinto an acid addition salt.

Cyanogen halides, particularly cyanogen chloride and cyanogen bromide,or esters of cyanic acid, particularly the phenyl ester are suitablereactive functional derivatives of cyanic acid. The reaction ispreferably performed in the presence of a Water miscible or waternon-miscible inert organic solvent in the presence or absence of water.Suitable inert organic solvents are, e.g., hydrocarbons such as benzene,toluene, or Xylene, lower alkanols such as methanol or ethanol,ether-type liquids such as diethyl ether, dioxane or tetrahydrofuran,chlorinated hydrocarbons such as methylene chloride, lower ketones, suchas acetone or methyl ethyl ketone, carbonic acid esters such as aceticacid ethyl ester, carbonic acid nitriles such as acetonitrile, orsulfones such as tetrahydrothiophene-1,ldioxide. The reaction can beperformed in the presence or absence of an acid binding agent. As acidbinding agents are suitable inorganic bases or salts, e.g. alkalihydroxides, alkali hydrogen carbonates, alkali carbonates or alkaliphosphates such as the corresponding sodium or potassium compounds. Alsosuitable are calcium carbonate, calcium phosphate and magnesiumcarbonate.

The hydrolysis or reduction of a masked amino group X" to the free aminogroup can be performed as described hereinbefore.

A first group of starting materials of Formula IV consists ofN-(Z-aminoethyl)-phenylsulfonamides, wherein phenyl is substituted inp-position by a group X" and the amino group is substituted by a group RThese starting materials are prepared by reacting a correspondinglysubstituted 1-phenylsulfonyl-aziridine with a primary amine NH R Suchaziridines have been described in the literature; e.g.4'-(aziridine-l-sulfonyl)-acetanilide is described by R. Lehmann et al.,Bull. Soc. Chim. Belges., 55, 5297 (1946); CA, 41, 5475f (1947) andl-phenylsulfonyl-aziridine by J. Nelles et al., Germ. 695,331. Furtheraziridines of this type can be prepared analogously.

A second group of starting materials of Formula IV corresponds to thefirst group, however has additionally a lower alkyl group R substitutedin the ethylene moiety. These compounds are prepared by reacting acorrespondingly substituted phenylsulfonyl chloride with a2-alkylaziridine [A. Weissberger, Heterocyclic Compounds with ThreeandFour-Membered Rings, part 1, John Wiley & Sons Inc., London (1964)] inthe presence of diluted sodium hydroxide solution. Substitutedl-phenylsulfonyl-Z- alkyl-aziridines are obtained which can be furtherreacted with primary amines NH R as described hereinbefore.

Starting materials of a third group of Formula IV wherein n is and R andR together form the tetramethylene group are prepared by condensingZ-aminocyclohexanol hydrochloride and N-acetyl-sulfanilyl chloride inpyridine to obtain N'-[Z-(p-acetamidophenylsulfonyloxy)-cyclohexyl]-N-acetylsulfanilamide and reacting the latter With a primary amine NH Rin ethanolic solution whereby the p-acetamidophenylsulfonyloxy group isreplaced by the -NHR group.

Compounds of Formula I wherein n is 0 are produced according to a thirdprocess by condensing and cyclising a compound of the formula wherein RR R and R have the meanings as defined in Formula I and X has themeaning as defined in Formula II, with a compound of the formula HNR CEN(VI) wherein R has the meaning as defined in Formula I, or with analkali or alkaline earth derivative thereof, if necessary hydrolysing orreducing the reaction product obtained to convert the masked amino groupX into the free amino group and, if desired, converting the reactionprodnet of Formula I, wherein n is 0, into an acid addition salt.

Suitable alkali and alkaline earth derivatives of Formula VI are thelithium sodium, potassium and calcium derivatives. The condensation ispreferably performed in an ether-type liquid, e.g. in ether,tetrahydrofuran, dioxane, anisole or ethylenglycol-dimethylether.

The masked amino groups X" are the same as described hereinbefore andthe conversion of these groups into the free amino group can beperformed also as described hereinbefore.

Starting materials of Formula V can be prepared as describedhereinbefore.

Compounds of Formula I are prepared according to a fourth process bycondensing and cyclising a compound of formula X S O 2NH2 (VII) whereinX has the meaning as defined in Formula II with a reactive ester of ahydroxy compound of formula wherein n, R R R R and R have the meaningsas defined in Formula I, where applicable hydrolysing or reducing thereaction product obtained to convert the masked amino group X" into thefree amino group and, if desired, converting the reaction product ofFormula I into an acid addition salt.

Suitable reactive esters of hydroxy compounds of Formula VIII are e.g.halogenides, particularly chlorides and bromides, or sulfonic acidesters such as methanesulfonic acid or oand p-toluene-sulfonic acidesters. The condensation is performed preferably in a solvent miscibleor not miscible with water and in the presence or absence of Water.Suitable solvents are e.g. alkanols such as butanol, ether-typesolvents, such as dioxane, diethyleneglycolmonomethylether, carbonicacid amides, such as N,N-dimethylformamide or sulfoxides such asdimethylsulfoxide. The condensation is advantageously carried out in thepresence of an acid binding agent. Such acid binding agents are named inthe first process of this invention. Furthermore also tertiary organicbases such as N,N-diisopropyl-ethyl-amine can be used.

Conversion of the masked amino group X" into the amino group can beperformed as described hereinbefore.

Reactive esters of the hydroxy compounds of Formula VIII to be used asstarting materials in this fourth process are prepared e.g. by reactingl-alkylaziridines with cyanogen halides in dioxane whereby thehalogenides of compounds of Formula VIII are obtained. Particularlyuseful in this reaction are cyanogen chloride and cyanogen bromide.

Compounds of Formula I are prepared according to a fifth process bycondensing and cyclising a reactive ester of a compound of the formulawherein n, R R R and K, have the meanings as defined in Formula I and X"has the meaning as defined in Formula II, with a primary amine NH Rwhere applicable hydrolysing or reducing the reaction product obtainedto convert the masked amino group X" into the free amino group and, ifdesired, converting the reaction product of Formula I into an acidaddition salt.

Suitable reactive esters of a hydroxy compound of Formula IX are, e.g.halogenides, particularly chlorides and bromides or sulfonic acid esterssuch as methanesulfonic acid or oand p-toluenesulfonic acid esters. Thecondensation is performed preferably in a solvent. Suitable solvents aresuch solvents as named in the fourth process of this invention.

Advantageously the reaction is performed in the presence of an acidbinding agent. Such agents are named also in the fourth process of thisinvention. Furthermore and preferably suitable acid binding agents arethe primary bases NH -R which are present in excess.

Conversion of the masked amino group X" into the free amino group can beperformed as described hereinbefore.

Reactive esters of the hydroxy compounds of Formula IX to be used asstarting materials in this fifth process are prepared, e.g. by reactionof cyanogen bromide with aziridine in ether to giveN-(2-bromoethy1)-cyanamides. The latter are reacted in acetone in thepresence of dilute sodium hydroxide solution with a correspondinglysubstituted phenylsulfonylchloride whereupon the correspondinglysubstituted N-(2-chloroethyl) -N-cyanophenylsulfonamides are obtained.

Compounds of Formula I are prepared according to a sixth process byreacting a compound of the formula wherein 12, R R R R and R have themeanings as defined in Formula I, X" has the meaning as defined inFormula II and R is arylmethyl, diarylmethyl or triarylmethyl, accordingto von Braun with a cyanogen halide, whereby R is replaced by the group-C=N, cyclising the intermediate product obtained, where applicablehydrolysing or reducing the reaction product obtained to convert theprotected amino group X" into the free amino group and, if desired,converting the reaction product of Formula I into an acid addition salt.

Suitable groups, R are e.g. the benzyl, benzhydryl, and the tritylgroup. Cyanogen chloride and cyanogen bromide are the preferred cyanogenhalides used in this process. The reaction is advantageously performedin a solvent. Suitable solvents are e.g. hydrocarbons, such as benzeneor toluene, or ether-type solvents such as ether, dioxane ortetrahydrofuran.

Conversion of the masked amino group X" into the free amino group can beperformed as described hereinbefore.

Compounds of Formula X to be used as starting materials in this sixthprocess are prepared, e.g. by reacting in dioxane-water correspondinglysubstituted l-phenylsulfonylaziridines of Formula V with amines of theformula wherein R and R have the meanings as defined in Formula X.

Compounds of Formula I are prepared according to a seventh process bythermal condensation and cyclisation of addition salts of the formulawherein 11, R R R R and R have the meanings as defined in Formula I, X"has the meaning as defined in Formula II, and y is chloro, bromo oriodo, where applicable converting the masked amino group X" into thefree amino group and, if desired, converting the reaction product ofFormula 1 into an acid addition salt.

The thermal condensation and cyclisation is performed by heating theaddition salt with or without a solvent. Suitable solvents are inertliquids with a high boiling point, e.g. ethers, such asdiethyleneglycoldimethylether, or carbonic acid amides, such asN,N-dimethyl-formamide.

Conversion of the masked amino group X" into the free amino group can beperformed as described hereinbefore.

Compounds of Formula XII to be used as starting materials in thisseventh process are prepared by reacting in water correspondinglysubstituted phenylsulfonyl chlorides with disodium cyanamide whereby thesodium derivatives of the corresponding N-cyano-phenylsulfonarnides ofFormula XIII GEN (XIII) are formed.

The latter are reacted with acid addition salts of the formula wherebythe desired addition salts of Formula X'I'I are formed. The symbols n, RR R R R X" and Y in Formulas XIII and XIV have the meanings as definedin Formula XII.

If desired, the compounds of Formula I obtained according to theprocesses of the invention are subsequently converted intopharmaceutically acceptable acid addition salts. These salts areproduced via conventional methods, e.g. by reacting the compounds of theFormula I with the equivalent amount of an acid in a suitableaqueous-organic or organic solvent such as methanol, ethanol, diethylether, chloroform or methylene chloride.

Suitable pharmaceutically acceptable acid addition salts are such saltswhich are derived from a compound of Formula I and a pharmaceuticallyacceptable acid, such as hydrochloric acid, hydrobromic acid, sulfuricacid, phosphoric acid, methane sulfonic acid, ethane sulfonic acid,fi-hydroxy-ethane sulfonic acid, acetic acid, lactic acid, oxalic acid,succinic acid, fumaric acid, maleic acid, malic acid, tartaric acid,citric aid, benzoi acid, salicylic acid, phenylacetic acid, mandelicacid and embonic acid.

The new compounds of the invention have been found to have hypoglycemicactivities. These hypoglycemic effects are illustratively demonstratedin rats by orally administering the test compound to groups of 5 to 6animals which have been not fed for 24 hours. Blood samples are takenfrom a vein of the animals and the blood sugar content is determinedaccording to the method of Hagedorn-Iensen with an autoanalyser. Thus itis shown that the compounds of the invention on oral administra- 9 tionin amounts of from 20 to 400 mg./kg. of bodyweight have significanthypoglycemic effects. Particular good blood sugar lowering propertieshave the following compounds:

1-sulfanilyl-2-imino-2-nbutyl-imidazolidine, 1- (p-chlorophenylsulfonyl-2-imino-3 -n-buty1-imidazolidine,.1-sulfanilyl-2-imino-3-n-butyl-5-ethyl-imidazolidine,1-sulfanilyl-2-imino-3-i=butyl-irnidazolidine,l-sulfanilyl-2-imino-3-i-propylimidazolidine,1-sulfanilyl-2-amino-3-t-butyl-imidazolidine,1-sulfanilyl-2-imino-3-cyclopentyl-imidazolidine, 1-sultanilyl-2-imino-3-n-butyl-4-methyl-imidazolidine,l-sulfanilyl-Z-imino-S-sec-butyl-4-methyl-imidazolidine, 1-sulfanilyl-3-imino3 -t-'butyl-4-methyl-imidazolidine,1-(p-methoxyphenylsulfonyl)-2-imino-3 -n-butylimidazolidine,1-(p-acetylphenylsulfonyl)-2-imino-3-n-butylimidazolidine and1-sulfanilyl-2-imino-3-t-butyl-4-methyl-imida-zolidine.

The toxicity of the compounds of the invention on oral administration isof favourable low order.

Safety and eifectiveness in humans has been demonstrated with1-sulfanilyl-2-imino-3-n-butyl-imidazolidine on oral administration topatients suifering from diabetes.

The new active substances are preferably administered orally. The dailydosages vary between about 1.5 and about 8 mg./ kg. of bodyweight foradult mammals. Suitable dosage units such as drages, tablets or capsulespreferably contain 50-500 mg. of an active substance according to theinvention, that is from 20 to 80% of a compound of Formula 1. Suchdosage units are produced by combining the active substance with, e.g.,solid, pulverulent carriers such as lactose, saccharose, sorbitol,mannitol; starches such as potato starch, maize starch or amylopectin;laminaria powder or citrus pulp powder; cellulose derivatives orgelatine, optionally with the addition of lubricants such as magnesiumor calcium stearate or polyethylene glycols of suitable molecularweights to form tablets or drage cores. The latter are coated with, erg.concentrated sugar solutions which can also contain, e.g. gum arabic,talcum and/or titanium dioxide, or with a lacquer dissolved in easilyvolatile organic solvents or mixtures of solvents. Dyestufl's can beadded to these coatings, e.g. to distinguish between varying dosages ofactive substance.

Other suitable dosage units for oral administration are hard or softgelatine capsules. The former contain the active substanceadvantageously in the form of a granulate optionally in admixture withdiluents such as maize tarch, and lubricants such as talcum or magnesiumstearate and, optionally stabilising agents such as sodium metabisulfite(Na S O or ascorbic acid. In soft capsules the active substance ispreferably dissolved or suspended in suitable liquids such as liquidpolyethylene glycols, to which stabilising agents can be added.

The following examples will serve to further typify the nature of thepresent invention but should not be construed as a limitation on thescope thereof. If not otherwise denoted by an alkyl group is mean astraight chain n-alkyl group.

EXAMPLE 1 (a) 355 g. of 1-butyl-2-amino-Z-imidazoline hydrochloride areadded in portions to a solution of 198 g. of sodium hydroxide in 2litres of water. A solution of 443 g. of pnitrobenzene sulphochloride in2 litres of acetone is then added dropwise within 15 minutes and the redreaction mixture obtained is heated for 3 hours at 70, whereupon theacetone distills off. The residue is poured onto ice and the crudeproduct is filtered off under suction. To purify, it is taken up in 2litres of 2 N hydrochloric acid, insoluble parts are filtered off andwashed with water and the free base is precipitated from thehydrochloric acid solution by pouring it onto ice and concentratedammonia. The precipitate is filtered off under suction, washed withwater and recrystallised from benzene. The pure 1(p-nitro-phenylsulphonyl)-2-imino-3-butyl-imidazolidine obtained meltsat 9899.

(b) 390 g. of the nitro compound produced according to (a) are dissolvedin 15 litres of ethanol and the nitro group is reduced with hydrogen at20 and normal pressure in the presence of platinum charcoal. Thecatalyst is filtered off and the filter residue is washed with ethanol.The filtrate is concentrated in vacuo, 1 litre of 2 N hydrochloric acidis added to the residue, the crude base, and the insoluble parts arefiltered off and washed with water. The pure base is precipitated incrystalline form from the hydrochloric acid filtrate with 2 N sodiumhydroxide solution. It is filtered oif under suction, washed with waterand dried in vacuo at The l-sulphanilyl-2-imino-3- butyl-imidazolidineobtained melts at 179-181".

EXAMPLE 2 (a) 60 ml. of 5 N sodium hydroxide and 30 g. of ice are addedto 20.5 g. of 1-cyclohexyl-2-amino-2-imidazoline hydrochloride and asolution of 26 g. of p-nitro-benzene sulphochloride in 100 ml. ofacetone is added to the mixture. The crude 1-(p-nitrophenylsulphonyl)-2-imino-3- cyclohexyl-imidazoline immediately crystallises. It isfiltered off under suction, washed with water and recrystallised from asmall amount of ethanol M.P. -161 with decomposition.

(b) 35.2 g. of the nitro compound produced according to (a) aredissolved in 1 litre of ethanol and the solution is hydrogenated withhydrogen at 20 and normal pressure, in the presence of palladiumcharcoal (50% palladium), until no more hydrogen is taken up. Thecatalyst is then filtered off and washed with ethanol and the filtrateis evaporated in vacuo. Recrystallisation of the residue fromdioxane/water yields pure 1-sulphanilyl-2-imino-3-cyclohexyl-imidazolidine, M.P. l8ll83.

EXAMPLE 3 (a) 10.0 g. of 1-butyl-2-amino-2-imidazoline hydrochloride areadded to 5.5 g. of sodium hydroxide in 55 ml. of water. 15 g. ofp-acetylamino-benzene sulphochloride dissolved in 100 ml. of warmacetone are added to the clear solution obtained whereupon thetemperature of the reaction mixture rises and a thick, white precipitateis formed. The mixture is heated for half an hour at 9095 and thenconcentrated in vacuo. The crystal slurry which remains is filtered offunder suction, washed with water and recrystallised from 1 litre ofethanol. Colourless p-(2- imino 3butyl-l-imidazolidinylsulphonyl)-acetanilide is obtained which melts at243-244.

(b) 15 g. of the acetanilide derivative produced according to (a) areheated in 50 ml. of 2 N hydrochloric acid for 1 hour at 80. The solutionis then cooled to 20 and made alkaline with 2 N sodium hydroxidesolution. The precipitate formed is filtered off under suction andwashed with water. The filter residue is recrystallised from ethanolwhereupon l-sulphanilyl-2-imino-3-butyl-imidazolidine is obtained, M.P.17918l.

EXAMPLE 4 (a) 10.0 g. of 1-butyl-2-amno-2-imidazo1ine hydrochloride areadded to 5 .5 g. of sodium hydroxide in 55 ml. of water. 12.5 g. ofN-methoxycarbonyl-sulphanil chloride in 100 ml. of acetone are added tothe clear solution obtained. The solution turns yellow for a short timewhereupon a thick, colourless precipitate immediately forms. 100 ml. ofwater are added to the mixture, the precipitate is filtered off andwashed with water. Recrystallised from methanol, the purep-(2-imino-3-butyl-l-imidazolidinylsulphonyl)-carbanilic acid ethylester obtained melts at 198-200.

(b) 17.7 g. of the methoxycarbonyl compound produced according to (a)are refluxed for 1 hour in 100 ml. of 90% methanol containing 6 g. ofsodium hydroxide. The reaction mixture obtained is concentrated in vacuoand 50 ml. of water are added. The crystalline precipitate formed isfiltered off under suction and washed with 100 ml. of water. Afterrecrystallisation from ethanol, the 1-sulphanilyl-2-imino-3-butyl-imidazolidine obtained melts at 179-181".

- EXAMPLE 5 4 (2-imino-3-sec. butyl-1-imidazolidinylsulphonyl)-acetanilide (M.P. 250-251) is obtained analogously to Example 3(a) fromg. of 1-sec. butyl-2-amino-2- imidazoline hydrochloride and g. ofp-acetylamino-benzene sulphochloride. It is hydrolysed according toExample 3(b) to form 1-sulphanilyl-2-imino-3-sec. butyl-imidazolidine,M.P'. 173-1735".

EXAMPLE 6 (a) 13.5 g. of 1-methyl-2-amino-2-imidazoline hydrochlorideare dissolved in 150 ml. of water and 14 g. of sodium hydroxide areadded. The solution of 23.4 g. of p-acetylaminobenbene sulphochloride in300 ml. of acetone is added whereupon an exothermic reaction occurs anda thick crystal slurry precipitates. The mixture is refluxed for 1 hour,cooled and diluted with 250 ml. of water. The crystals are filtered offand recrystallised from dimethyl formamide/water. 1(p-acetamidophenylsulphonyl) 2 imino-3-methyl-imidazolidine melts at278- 279.

(b) 29.6 g. of 1 (p-acetamidophenylsulphonyl)-2-imino-B-methyl-imidazolidine are dissolved in 240 ml. of 2 Nhydrochloric acid and the solution is heated at 80 for 30 minutes. Aftercooling, the solution is stirred into 300 ml. of 2 N sodium hydroxidesolution. The precipitated crystals are filtered off and recrystallisedfrom methanol/water. The pure 1sulphanilyl-2-imino-3-methylimidazolidine melts at 209-210.

EXAMPLE 7 EXAMPLE 8 1 (p-acetamidophenylsulphonyl) 2imino-3-cyclohexen-l-yl-imidazolidine is obtained analogously to Example6 from 20.2 g. of 3 cyclohexen-1-yl-2-amino-2- imidazoline hydrochloridein 150 ml. of water and 10 g. of sodium hydroxide solution with 23.4 g.of p-acetamidobenzene sulphochloride in 300 ml. of acetone. It issaponified by heating at 80" for 30 minutes in 2 N hydrochloric acid toform 1 sulphanilyl-2-imino-3-cyclohexen-l-ylimidazolidine.

EXAMPLE 9 (a) 31.3 g. of N -(2-butylamino-ethyl)-N-acetyl-sulphanilamide are dissolved in 100 ml. of 2 N sodium hydroxidesolution and 10.6 g. of cyanogen bromide is added with cooling at -30".The crude product precipitates as crystals. .It is filtered by suctionafter minutes and recrystallised from N,N-dimethylformamide. Theresulting 4'-(2 irnino-3-butyl-imidazolidin-1-ylsulphonyl)- acetanilidemelts at 243-244".

(b) 33.8 g. of the acetanilide obtained according to (a) are heated with100 ml. of 2 N hydrochloric acid for one hour to 80. The reactionmixture is then cooled to 20 and rendered alkaline with 2 N sodiumhydroxide solution. The crude base which precipitates is removed byfiltration, washed with water and recrystallised from ethanol.

12 The resulting 1-sulphanilyl-2-imino-3-butyl-imidazolidine melts at179-181".

(c) The starting compound for (a) is obtained as follows:

24.0 g. of 4'-(aziridin-l-ylsulphonyl)-acetanilide [cf. R. Lehmann etal., Bull. Soc. Chim. Belges, 55, 52-97 (1946); C.A., 41, 5475f (1947)]are dissolved in the cold in 100 ml. of dioxane and 15 ml. of water andthe solution is added dropwise to 100 ml. of butylamine. The reactionmixture is then refluxed for one hour and the excess butylamine as wellas the dioxane is removed by distillation. The crystalline residue isrecrystallised from ethyl acetate to yield pure N -(2butylamino-ethyl)-N -acetyl-sulph anilamide melting at 97-98".

EXAMPLE 10 (a) Analogously to Example 9(a), 4'-(2-irnino-3-methyl-imidazolidin-l-ylsulphonyl)-'acetanilide having a melting pointof 266-267 is obtained from 27.1 g. of N (2-methylamino-ethyl) -N-acetyl-sulphanilamide and 10.6 g. of cyanogen bromide.

(b) 29.6 g. of the acetanilide obtained according to (a) are allowed tostand for 48 hours at 20 with 200 ml. of 8 N ethanolic hydrochloricacid. The reaction mixture is then concentrated under vacuum, thecrystalline residue is dissolved in water, and the solution is renderedalkaline with 2 N sodium hydroxide solution. The crude free baseprecipitates; it is filtered by suction and recrystallised frommethanol/water to yield the pure 1-sulphanilyl-2-imino-3-methyl-imidazolidine melting at 209-211".

(c) The starting material used under (a), namely N(Z-methylamino-ethyl)-N -acetyl-sulphanilamide having a melting point of100-102 (from ethyl acetate), is obtained analogously to Example 9(c)from 24 g. of 4- aziridin-l-ylsulphonyl)-acetanilide and 100 ml. ofaqueous rnethylarnine.

EXAMPLE 1 1 (a) Analogously to Example 9(a), 4'-(2-imino-3-tert. butyl-Smethyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P. 227-229", isobtained from 32.7 g. of N -(l-methyl- 2-tert. butylamino-ethyl)-Nacetyl-sulphanilamide and 10.6 g. of cyanogen bromide.

(b) 35.2 g. of the acetanilide obtained according to (a) are added withstirring to 125 g. of sulphuric acid which has been heated to 40. Themixture is heated for 2 hours at 50" and the solution is poured withstirring into 750 ml. of water. The crude product precipitates as thesulphate. The pH of the reaction mixture is adjusted to 6.3 with 10 Nsodium hydroxide solution. The mixture, with the exception of a slightimpurity, dissolves completely; it is stirred for 15 minutes with 2 g.of active charcoal and filtered over Hyfio (purified diatomaceousearth). The filtrate is rendered alkaline with 10 N sodium hydroxidesolution. The crude product precipitates. It is filtered, washed withwater, dried at and recrystallised from ethyl acetate. The resulting1-sulphanilyl-2-imino-3- tert. butyl-S-methyl-imidazolidine melts at145-146".

(c) The starting compound mentioned under (a) is obtained as follows: Asolution of 23.3 g. of N-acetyl-sulphanilyl-chloride in 70 ml. ofacetone is added dropwise with stirring at 10 to 0 to 5 .6 g. of2-methyl-aziridine in 30 ml. of 4 N sodium hydroxide solution. Thereaction is stirred at 0" for 2 more hours and then poured on to 400 ml.of ice water. The resulting suspension is filtered, the precipitate,crude 4-(2-methyl-aziridin-l-ylsulphonyl)- acetanilide, is washed withwater and then further processed immediately, since it polymeriseseasily.

(d) The crude product obtained according to (c) is converted analogouslyto Example 9(c) with ml. of tert. butylamine to N -(1-methyl-2-tert.butylamino-ethyl) N -acetyl-sulph'anilamide, M.P. 93-95".

EXAMPLE 12 (a) A solution of 11.3 g. of cyanogen bromide in 11.5 ml. ofether is added dropwise during 10 minutes to a solution of 34 g. of N-acetyl-N -[2-(3-ethoxy-propylamino)-ethyl]-sulphanilamide in 175 ml. ofdioxane. The resulting emulsion is refluxed in a bath of 70 for 1 /2hours. The reaction mixture is then concentrated. The residual yellowresin is dissolved in 175 ml. of water, the colour of the solution isremoved with active charcoal, the solution is filtered and renderedalkaline at with 2 N sodium hydroxide solution. The precipitatedcrystals are separated by filtration, washed with water andrecrystallised from ethanol, yelding 4-[2-imino-3-(3-ethoxy-propyl]-imidazolidin-l-ylsulphonyl) acetanilide, M.P. 223-225 (b)36.8 g. of the acetanilide obtained according to (a) are dissolved whilestirring for 15 minutes in 200 ml. of 8 N ethanolic hydrochloric acid.The solution is allowed to stand at room temperature for about 80 hours,and then concentrated. The residual brown resin is dissolved in water,the colour of the solution is removed with act ve characoal, and thesolution is filtered. The clear filtrate which has been cooled with iceis carefully rendered alkaline with concentrated sodium hydroxidesolution and the product which precipitates, crystallising after severalminutes, is separated by filtration, washed with water and dried. Theresulting 1-sulphanilyl-2-amino-3-(3-ethoxypropyl)-imidazolidine meltsafter recrystallisation from ethanol at 148-150.

(c) The starting product for (a) is obtained as follows: 200 ml. of3-ethoxy-propylamine are heated to 80 and then while stirring 24.0 g. of4-(aziridin-l-ylsulphonyl)-acetani1ide in 128 ml. of dioxane/water (921)are added thereto during 30 minutes. The yellow solution is then heatedat 80 for another 1 /2 hours and then concentrated. The residual oil ispurified by elution chromatography on a column of 400 g. of silica gel.The N,N-bis-[2-(N -acetyl-sulphanilamido) ethyl]-3-ethoxypropyl-am ne isfirst eluted with chloroform/ethanol (9:1), and then the N -acetyl-N-[2-(3-ethoxy-propylamino)-ethyl]-sulphanilamide which is obtained as anoil is eluted with chloroform/ethanol (9: 1) and (4:1).

EXAMPLE 13 (a) Analogously to Example 12(a), 4-hexahydro-2- imno-benzimdazolin 1 ylsulphonyDacetanilide is obtained from 42.6 g. of N-(2-benZylamino-cyclohexyl)- N -acetyl-sulphanilamide and 10.6 g. ofcyanogen bromide. (b) 42.7 g. of the crude acetanilide obtainedaccording to (a) are hydrolysed analogously to Example 10(b) with 200ml. of ethanolic hydrochloric acid to yield l-sulphanilyl-Z-imino 3benZyl-hexahydro-benzimidazoline, M.P. 208-210.

(c) The starting material for (a) is obtained as follows: 15.15 g. of2-amino-cyclohexanol-hydrochloride are suspended in 120 ml. of absolutepyridine and the suspension is cooled to 5. During half an hour 55.0 g.of N-acetyl-sulphanilyl chloride are introduced into this mixture at -5to 0. A slightly exothermic reaction takes place and the suspensiondissolves. The solution is stirred for 4 hours at 0-5 in an ice bath andthen poured on to 900 ml. of ice water. A yellow sticky crude productprecipitates; the crude product is extracted three times with ethylacetate. The organic extract is washed once with water, twice with 6 Nhydrochloric acid and twice with water, dried over sodium sulphate andconcentrated. Recrystallisation of the crystalline residue from methanolyields pure N -[2-(p-acetamido phenylsulphonyloxy)- cyclohexyl] -N-acetyl-sulphanilamide.

(d) 50.9 g. of the sulphanilamide obtained according to (c) aresuspended in 250 ml. of ethanol and treated with 157 g. of benzylamine.The mixture dissolves and a slightly exothermic reaction takes place.The solution is allowed to stand for 2 hours at room temperature, it isthen heated for 4 hours to 50 and finally concentrated. The residue istaken up in methylene chloride and concentrated ammonia and the organicphase is extracted w th 2 N hydrochloric acid. The hydrochloric acidextract is purified with active characoal and filtered. The filtrate istreated with ammonia; a resin precipitates. Several drops of methylenechloride are added to the resulting suspension and the resin istriturated; it then crystallises. The crystals are filtered, washed withwater and recrystallised from isopropanol/methylene chloride. N-(2-benzylamino-cyclohexyl) N acetyl-sulphanilamide having a meltingpoint of 180-182 is obtained.

EXAMPLE 14 (a) Analogously to Example 9(a), starting from 28.5 g. of N-(Z-ethylamino-ethyl)-N -acetyl-sulphanilamide, M.P. 108-110 (from ethylacetate), and 10.6 g. of cyanogen bromide, 4-(2-imino-3-ethylimidazolidin-lylsulphonyl)-acetanilide, M.P. 267-269 (from ethanol), isobtained. 31.0 g. of the latter are hydrolysed analogously to Example9(b) with ml. of 2 N hydrochloric acid to give1-sulphanilyl-2-imino-3-ethyl-imidazolidine, M.P. 171-172" (frommethanol/water), as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.0 g. of 4'-(aziridin-1- ylsulphonyU'acetanilide and 100 ml.of ethylamine.

EXAMPLE 15 (a) Analogously to Example 9(a), starting from 29.7 g. of N-(2-allylamino-ethyl)-N -acetyl sulphanilamide (crude product), and 10.6g. of cyanogen bromide, 4- (2-imino-3-allyl-imidazolidin-l-ylsulphonyl)acetanilide, M.P. 247-249 (from methanol), is obtained. 32.2 g. of thelatter are hydrolysed analogously to Example 9(b) with 100 ml. of 2 Nhydrochloric acid to give 1-sul- M.P. 158-160 (from methanol/ water) asend product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.0 g. of 4'-(aziridin-1- ylsulphonyl)-acetanilide and ml. ofallylamine.

EXAMPLE 16 (a) Analogously to Example 9(a), starting from 29.9 g. of N-(2-propylamino-ethyl) N acetyl-sulpham'liamide, M.P. 89-90 (from ethylacetate), and 10.6 g. of cyanogen bromide,4'-(2-imino-3-propyl-imid'azo1idin-1- ylsulphonyl)-acetanilide, M.P.253-255 is obtained. 32.4 g. of the latter are hydrolysed analogously toExample 10(b) with 8 N ethanolic hydrochloric acid to give1-sulphanilyl-2-imino-3-propyl-imidazolidine, M.P. 164-166 (frommethanol), as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.4 g. of 4'-(aziridin-1- ylsulphonyl)-acetanilide and 100ml. of propylamine.

EXAMPLE 17 (a) Analogously to Example 9(a), starting from 29.9 g. of N(2 isopropylamino-ethyl)-N -acetyl-sulphanilamide, M.P. 91-93 (fromethyl acetate), and 6.2 g. of cyanogen chloride,4'-(2-imino-3-isopropyl-imidazo1idinl-ylsulphonyl)-acetanilide, M.P.253-254, is obtained. 32.4 g. of the latter are hydrolysed analogouslyto Example 10(b) with 200 ml. of 8 N ethanolic hydrochloric acid to give1-sulphanilyl-2-imino-3-isopropyl-imidazolidine, M.P. 183-184", as endproduct.

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.0 g. of 4'-aziridin-1-y1- sulphonyl)-acetanilide and 100ml. of isopropylamine.

EXAMPLE 18 (a) Analogously to Example 9(a), starting from 31.3 g. of N-(2-isiobutylamino-ethyl)-N -acetyl-sulphanilamide, M.P. 7073 (fromethyl acetate/ether), and 10.6 g. of cyanogen bromide,4'-(2-imino-3-isobutylimidazolidin-l-ylsulphonyl)-acetanilide, M.P.264-265 (from methanol), is obtained. 33.8 g. of the latter arehydrolysed analogously to Example 10(b) with 200 ml. of 8 N ethanolichydrochloric acid to give l-sulphanilyl- 152-imino-3-isobuty1-imidazo1idine, M.P. 146-l47 (from methanol), as endproduct.

(b) The starting material for (a) is obtained analogously to Example9(c) from 27.6 g. of N -(2-ch1or0- ethyl)-N -acetylsulphanilamide and100 ml. of isobutylamine.

EXAMPLE 19 (a) Analogonsly to Example 9(a), starting from 31.3 g. of N-(2-sec. butylamino-ethyl) N acetyl-sulphanilamide, M.P. 70-72, and 10.6g. of cyanogen bromide, 4' (2-imino-3-sec.butylimidazolidin-l-ylsulphonyl)-acetanilide, M.P. 265-266 (frommethanol), is obtained 33.8 g. of the latter are hydrolysed analogouslyto Example 10(=b) with 200 ml. of 8 N ethanolic hydrochloric acid toyield the end product, 1-sulphanilyl-2-imino-3-sec. butyl-imidazolidine,M.P. 173-173.5 (from methanol).

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.0 g. of 4'-(aziridin-1- ylsulphonyl)-acetanilide and 100ml. of sec. butylamine.

EXAMPLE 20 (a) Analogonsly to Example 9(a), starting from 31.3 g. of N-(2-tert. butylamino-ethyl)-N -acetyl-sulphanilamide, M.P. 98-101 (fromethyl acetate), and 6.5 g. of cyanogen chloride in place of cyanogenbromide, 414(2- imino 3 tert. butylimidazolidin l ylsulphonyl)-acetanilide, M.P. 245-247 (from methanol/water), is obtained. 33.8 g. of thelatter are hydrolysed analogously to Example 9(b) with 100 ml. of 2 Nhydrochloric acid to yield l-sulphanilyl 2 imino-3-tert.butylimidazolidine, M.P. 187189 (from methanol/Water), as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.0 g. of 4-(aziridin-1- ylsulphonyl)-acetanilide and 100 ml.of tert. butylamine.

EXAMPLE 21 (a) Analogonsly to Example 9(a), starting from 32.7 g. of N-(2-pentylamino-ethyl)-N -acetyl-sulphanilamide, M.P. 103-l04 (fromethyl acetate), and 10.6 g. of cyanogen bromide, 4'-(2-imino 3pentyl-imidazolidinl-ylsulphonyl)-acetanilide, M.P. 248-250" (frommethanol), is obtained. 35.2 g. of the latter are hydrolysed analogouslyto Example 9(b) with 100 ml. of 2 N bydrochloric acid to obtain1-sulphanilyl-2-imino-3-pentylimidazolidine, M.P. 167-168 (frommethanol), as end product.

(b) The starting material is obtained analogously to Example 9(c) from24.0 g. .of 4'-(aziridin-l-ylsulphonyl)- acetanilide and 100 ml. ofpentylamine.

EXAMPLE 22 (a) Analogonsly to Example 9(a), starting from 34.1 g. of N-(2-hexylamino-ethyl) N acetyl-sulphanilamide, M.P. 98-99 (from ethylacetate), and 11.9 g. of phenyl cyanate in place of cyanogen bromide,4'-(2- imino-3-imidazolidin 1 ylsulphonyl)-acetanilide, M.P. 236-238, isobtained. 36.6 g. of the latter are hydrolysed analogously to Example10(b) with 200 ml. of ethanolic hydrochloric acid to obtain1-sulphanilyl-2-imino-3-hexylimidazolidine, M.P. 182-183 as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) :from 24.0 g. of 4-(aziridin-1-ylsulphonyl)-acetanilide and 200 ml.of hexylamine.

EXAMPLE 23 (a) Analogonsly to Example 9(a), starting from 36.9 g. of N-(2-octylamino-ethyl)-N -acety1-sulphanilamide, M.P. 83-84 (from ethylacetate), and 10.6 g. of cyanogen bromide, 4'-(2-imino 3octyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P. 229-230 (frommethanol), is obtained. 39.4 g. of the latter are hydrolysed analogouslyto Example 10( b) with 200ml. of 8 N ethanolic hydrochloric acid toobtain 1-sulphanilyl-2-imino-3-octylimidazolidine, M.P. 143-144", as endproduct.

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.0 g. of 4'-(aziridinl-ylsulphonyl)-acetanilide and 150 ml.of octylamine.

EXAMPLE 24 (a) Analogonsly to Example 9(a), starting from 39.7 g. of N-(2-decylamino-ethyl)-N -acetyl-sulphanilamide, M.P. 87-88 (from ethylacetate), and 11.9 g. of phenyl cyanate in place of cyanogen bromide,4'-(2.-imino-3- imidazolidin-l-ylsulphonyl)-acetanilide, M.P. 216-217",is obtained. 42.2 g. of the latter are hydrolysed analogously to Example10(b) with 200 ml. of ethanolic hydrochloric acid to obtainl-sulphanilyl-2-imino-3-decylimidazolidine, M.P. 119-120".

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.0 g. of 4'-(aziridin-lylsulphonyl)-acetanilide and 200 ml.of decylamine.

EXAMPLE 25 (a) Analogonsly to Example 9(a), starting (from 42.5 g. of N-(dodecylamino-ethyl)-N -acetyl-sulphanilamide (crude product) and 10.6g. of cyanogen bromi-de, 4-(2- imino-3-dodecyl-imidazolidin 1ylsulphonyl)-acetanilide, M.P. 218-219 (from dioxane), is obtained. 45.0g. of the latter are hydrolysed analogously to Example 10(b) with 200ml. of ethanolic hydrochloric acid to obtain1-sulphanily1-2-imino-3-dodecyl-imid'azolidine, M.P. 111 (from ethylacetate), as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.0 g. of 4'-(aziridin-1- ylsulphonyl)-acetanilide and 200ml. of dodecylamine.

EXAMPLE 26 (a) Analogonsly to Example 9(a), starting from 32.5 g. of N-(2-cyclopentylamino-ethyl)-N -acetyl-sulphanilamide (M.P. of thehydrochloride: 215-217), and 10.6 g. of cyanogen bromide,4'-(2-imino-3-cyclopentyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P.261-263, is obtained. 35.0 g. of the latter are hydrolysed analogouslyto Example 9(b) with 100 ml. of 2 N hydrochloric acid to obtain1-sulphanilyl-2-imino-3-cyclopentyl-imidazo1- idine, M.P. 192-193", asend product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.0 g. of 4'-(aziridin-1- ylsulphonyl)-acetanilide and 100ml. of cyclopentylamine.

EXAMPLE 27 (a) Analogonsly to Example 9(a), starting from 33.9 g. of N-(Z-cyclohexylamino-ethyl)-N -acetyl-sulphanil amide, M.P. 136 (fromethyl acetate), and 10.6 g. of cyanogen bromide,4'-(2-imino-3-cyclohexyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P.283-284 (from methanol), is obtained. 36.4 g. of the latter arehydrolysed analogously to Example 9(b) with 100 ml. of 2 N hydrochloricacid to obtain 1-sulphanilyl-2-imino-3-cyclohexylimidazolidine, M.P.178-179, as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.0 g. of 4'-aziridin-1-ylsulphony1)-acetanilide and 100 ml.of cyclohexylamine.

EXAMPLE 28 1 7 EXAMPLE 29 (a) Analogously to Example 9(a), starting from39.0 g. of N -[2-(1-adamantylamino)-ethyl] N acetyl-sulphanilamide(crude product) and 10.6 g. of cyanogen bromide, 4'- [2-imino-3- 1-adamantyl) -irnidazolidin-l-ylsulphonylJ-acetanilide, M.P. 240-243, isobtained. 29.6 g. of the latter are hydrolysed analogously to Example(b) with 200 ml. of 8 N ethanolic hydrochloric acid to obtainl-sulphanilyl-2-imino-3-(l-adamantyD-imidazolidine, M.P. 240-243", asend product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 24.0 g. of 4-(aziridin-1- ylsulphonyl)-acetanilide and 15.0 g.of l-amino-adamantane.

EXAMPLE 30 (a) Analogously to Example 12(a), starting from 33.1 g. of N[2- (Z-methylthio-ethylamino -ethyl] -N -acetyl sulphanilamide (crudeproduct) and 10.6 g. of cyanogen bromide, 4[2-imino-3-(2-methylthio-ethy1) -imidazolidinl-ylsulphonyl]-acetanilide,M.P. 257-259, is obtained. 35.6 g. of the latter are hydrolysedanalogously to Example 12(b) with 200 ml. of 8 N ethanolic hydrochloricacid to obtain1-sulphanilyl-2-imino-3-(Z-methylthioethyl)-imidazolidine, M.P.153-155", as end product.

(b) The starting material for (a) is obtained analogously to Example12(c) from 24.0 g. of 4-(aziridin-1- ylsulphonyl)-acetanilide and 200ml. of 2-methylthioethylamine.

EXAMPLE 31 (a) Analogously to Example 12(a), starting from 31.5

g. of N -[2-(2-methoxy-ethylamino)-ethyl] -N -acetyl sulphanilamide(crude product) and 10.6 g. of cyanogen bromide,4-[2-imino-3-(2-methoxy-ethyl)-imidazolidinl-ylsulphonyl]-acetanilide,M.P. 230-232, is obtained. 34.0 g. of the latter are hydrolysedanalogously to Example 12(b) with 200 ml. of 8 N ethanolic hydrochloricacid to obtain 1-sulphanilyl-2-imino-3-(2-methoxy-ethyl)- imidazolidine,M.P. 159-161", as end product.

(b) The starting material for (a) is obtained analogously to Example12(c) from 24.0 g. of 4'-(aziridin-1 ylsulphonyl)-acetanilide and 200ml. of 2-methoxy-ethylamlne.

EXAMPLE 32 (a) Analogously to Example 12(a), starting from 32.9 g. of N-[2-(3-methoxy-propylamino)-ethyl]-N -acetylsulphanilamide (crudeproduct) and 10.6 g. of cyanogen bromide, 4'- [2-imino-3(3-methoxy-propyl) -imidazolidinl-ylsulphonyl]-acetanilide, M.P.233-235", is obtained. 35.4 g. of the latter are hydrolysed analogouslyto Example 12(b) with 200 ml. of 8 N ethanolic hydrochloric acid toobtain l-sulphanilyl-2-imino-3-(3-methoxy-propyl)-imidazolidine, M.P.132-134", as end product.

(b) The starting material for (a) is obtained analogously to Example12(c) from 24.0 g. of 4'-(aziridin-1- ylsulphony1)-acetanilide and 200ml. of 3-methoxy-propylamine.

EXAMPLE 3 3 (a) Analogously to Example 12(a), starting from 35.7 g. of N[2- (3 -isopropoxy-propylamino -ethyl] -N -acetylsulphanilamide (crudeproduct) and 10.6 g. of cyanogen bromide, 4- [2-imino-33-isopropoxy-propyl) -imidazolidine-l-ylsulphonyl]-acetanilide, M.P.224-226, is obtained. 38.2 g. of the latter are hydrolysed analogous toExample 12(b) with 200 ml. of ethanolic hydrochloric acid to obtain1-sulphanilyl-2-imino-3-(3-isopropoxypropyl)-imidazolidine, M.P.133-135, as end product.

(b) The starting material for (a) is obtained analogously to Example12(c) from 24.0 g. of 4-(aziridin-1- ylsulphonyl)-acetanilide and 200ml. of 3-isopropoxypropylamine.

EXAMPLE 34 (a) Analogously to Example 12(a), starting from 37.1

(a) Analogously to Example 9(a), starting from 28.5 g. of N-(1-methy1-2-methylamino-ethyl)-N -acetyl-sulphanilamide (crude product)and 10.6 g. of cyanogen bromide, 4-(2-irnino-3,S-dimethyl-imidazolidin lylsulphonyl)-acetanilide, M.P. 258-260", is obtained. 31.0 g. of thelatter are hydrolysed analogously to Example 11 (b) with 125 g. of 50%sulphuric acid to obtain l-sulphanilyl-2-imino-3,5-dimethyl-imidazolidine, M.P. 196-197, as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 25.4 g. of 4-(2-methyl aziridin-l-ylsulphonyl)-acetanilide[cf. Example 11(c)] and 200 ml. of 33% methylamine in ethanol.

EXAMPLE 3 6 (a) Analogously to Example 9(a), starting from 29.9 g. of N-(1-methyl-2-ethylamino-ethyl) N acetyl-sulphanilamide (crude product)and 10.6 of cyanogen bromide, 4'(2-imino-3-ethyl-S-methyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P.229-230, is obtained. 32.4 g. of the latter are hydrolysed analogouslyto Example 11(b) with 125 g. of 50% sulphuric acid to obtainl-sulphanilyl- 2-imino-3-ethy1-S-methyl-imidazolidine, as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 25.4 g. of 4-(2-methylaziridin-l-ylsulphonyl)-acetani1ide [cf.Example 11(c)] and 250 ml. of 20% ethylamine in benzene.

EXAMPLE 37 (a) Analogously to Example 9(a), starting from 31.3 g. of N-(l-methyl-2-propylamino-ethyl) N acetyl-sulphanilamide, M.P. 162-163,and 10.6 g. of cyanogen bromide,4-(2-imino-3-propyl-5-methyl-imidazolidin-l-ylsulphonyD-acetanilide,M.P. 254-255 is obtained. 33.8 g. of the latter are hydrolysedanalogously to Example 11(b) with 125 g. of 50% sulphuric acid to obtainl-sulphanilyl-2-imino-3-propy1- 5 methyl-imidazolidine, M.P.

146-148", as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 25.4 g. of 4'-(2-methylaziridin-l-ylsulphonyl)-acetanilide(cf. Example l1(c)] and ml. of propylamine.

EXAMPLE 3 8 (a) Analogously to Example 9(a), starting from 32.7 g. of N-(1-methyl-2-butylamino-ethyl) N acetyl-sulphanilamide, M.P. 166-167",and 10.6 g. of cyanogen bromide,4'-(2-imino-3-butyl-S-methyl-imidazolidin-l-ylsulphony1)-acetanilide,M.P. 243-244, is obtained. 35.2 g. of the latter are hydrolysedanalogously to Example 11*(b) With g. of 50% sulphuric acid to obtainl-sulphanilyl-Z-imino-3-butyl 5 methyl imidazolidine, M.P. 125-126, asend product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 25.4 g. of 4-(2-methylaziridin-l-ylsulphonyl)-acetanilide [cf.Example 11(c)] and 100ml. of butylamine.

EXAMPLE 39 (a) Analogously to Example 9(a), starting from 32.7 g. of N-(l-methyl-2-sec. butylamino-ethyl)-N -acety1- sulphanilamide, M.P.118-120, and 10.6 g. of cyanogen 19 bromide, 4'-(2-imino-3- sec.butyl-S-methyl-imidazolidinl-ylsulphonyl)-acetanilide, M.P. 242244, isobtained. 35.2 \g. of the latter are hydrolysed analogously to Example11 (b) with 125 g. of 50% sulphuric acid to obtain1-su1phanilyl-2-imino-3-sec. butyl-S-methyl-imidazolidine, M.P. 194195,as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 25.4 g. of 4'-(2-methylaziridin-l-ylsulphonyl)-acetanilide [f.Example 11(0)] and 100 ml. of sec. butylamine.

EXAMPLE 40 (a) Analogously to Example 9(a), starting from 34.1 g. of N-(l methyl 2 pentylamino-ethyl)-N --acetylsulphanilamide (crude product)and 10.6 g. of cyanogen bromide, 4'- (2-imino-3-penthyl-S-methyl-imidazolidinlylsulphonyl)-acetanilide, M.P. 228-229,is obtained. 36.4 g. of the latter are hydrolysed analogously to Example11(b) with 125 g. of 50% sulphuric acid to obtain1-sulphani1yl-2-imino-3-pentyl methyl-imidazolidine, M.P. 127-128", asend product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 25.4 g. of 4'-(2-methylaziridin-l-ylsulphonyl)-acetanilide[cf. Example 11(0)] and 100 ml. of pentylamine.

EXAMPLE 41 (a) Analogously to Example 9(a), starting from 38.3 g. of N-(l-methyl 2 octylamino-ethyl) -N -a0etyl-sulphanilamide, M.P. 87, and10.6 g. of cyanogen bromide, 4-(2-imino-3-octyl 5methyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P. 2l5-2l6, isobtained. 40.6 g. of the latter are hydrolysed analogously to Example11(b) with 125 g. of 50% sulphuric acid to obtain l-sulphanilyl-2-imino-3-octyl-S-methyl-imidazolidine, M.P. 108-109", as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 25.4 g. of 4-(2-methyl aziridin-l-ylsulphonyl)-acetanilide[cf. Example 11(0)] and 100 ml. of octylamine.

EXAMPLE 42 (a) Analogously to Example 9(a), starting from 35.1 g. of N-(1-methyl-2-cyclohexylamino-ethyl)-N -acetylsulphanilamide (crudeproduct) and 10.6 g. of cyanogen bromide,4'-(2-imino-3-cyclohexyl-S-methyl-imidazolidinl-ylsulphonyl)-acetanilide,M.P. 235237, is obtained. 37.6 g. of the latter are hydrolysedanalogously to Example 1l(b) with 125 g. of 50% sulphuric acid to obtainl-sulphanilyl-Z-imino 3 cyclohexyl-S-methyl-imidazoildine, M.P.217-218", as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 25.4 g. of 4-(2-methylaziridin-l-ylsulphonyl)-acetanilide [0f.Example 11(0)] and 100 ml. of cyclohexylamine.

EXAMPLE 43 (a) Analogously to Example 9(a), starting from 34.9 g. of N-[1-methyl-2-(3-cyclohexen-l-ylamino)-ethyl]- N -acetyl-sulphanilamide,M.P. 139-141", and 10.6 g. of cyanogen bromide, 4'- [2-imino-3-(3-0yclohexen-1-yl) -5- methyl-imidazolidin 1 ylsulphonyl]-acetanilide,M.P. 208209, is obtained. 37.4 g. of the latter are hydrolysedanalogously to Example 11'(b) with 125 g. of 50% sulphuric acid toobtain 1-sulphanilyl-2.-imino-3-(3-cyclohexen 1 yl) imidazolidine, M.P.208-209", as end product.

(b) The starting material for (a) is obtained analogously to Example9(c) from 25.4 g. of 4'-(2-methylaziridin-1ylsulphonyl)-acetanilide [cf.Example 11(0)] and 100 ml. of (3-cyclohexen-1-yl)-amine.

EXAMPLE 44 (a) A solution of 11.9 g. of phenyl cyanate in 50 ml. ofether is added during minutes with cooling at 10 to a solution of 25.5g. of N -(Z-cyclopropylamino-ethyl)- sulphanilamide in ml. of dioxane.The resulting suspension is refiuxed for 1% hours and then concentratedunder vacuum. The residue is treated with methylene chloride and 2 Nsodium hydroxide solution. The insoluble crude product is separated byfiltration; the organic phase of the filtrate is separated, dried oversodium sulphate and concentrated under vacuum. The residue is combinedwith the crude product obtained above and the mixture is recrystallisedfrom methanol to yield l-sulphanil-2-imino-3-cyclopropyl-imiazolidinemelting at 202 204.

The starting material is produced as follows:

(b) 7.1 g. of 1-sulphanilyl-aziridine, M.P. 124-126 produced bycatalytic reduction of l-(p-nitro-phenylsulphonyl)-aziridine with Raneynickel in dioxane [cf. R. Lehmann et al., Bull. Soc. Chim. Belges, 55,52 (1946)], is dissolved in 70 ml. of dioxane and this solution is addeddropwise during one hour to 18.2 g. of boiling cyclopropylamine. Themixture is refluxed for another 2 hours. The excess cyclopropylamine isthen removed by distillation and the reaction mixture is concentratedunder vacuum. The residue is recrystallised from ethyl acetate to obtain[N (2 cyclopropylamino-ethyl)-su phanilamide, M.P. 9l94.

EXAMPLE 45 (a) Analogously to Example 44(a), starting from 27.1 g. of N-(2-butylamino-ethyl)-sulp'hanilamide, M.P. 76- 78, and a solution of11.9 g. of phenyl cyanate in 50 ml. of ether,1-sulphanilyl-2-imino3-butylimidazolidine, M.P. l79-l8l, is obtained.

The starting material is produced as follows:

(b) 31.3 g. of N -(2-butylamino-ethyl) N acetylsulphanilamide are shakenwith 300 ml. of ethanolic hydrochloric acid. First of all the crystalsdissolve and then after an interval of several minutes, crystals againprecipitate. The suspension is allowed to stand for 16 hours at roomtemperature and then concentrated under vacuum. The residue is dissolvedin a little water, and carefully adjusted to a pH of 8 with 2 N sodiumhydroxide solution, whereby the solution becomes milky turbid. Thesolution is extracted three times, using 200 n11. of chloroform eachtime. The chloroform solution is Washed with a little water, dried withsodium sulphate and concentrated. The residue is recrystallised fromethyl acetate, to obtain N -(2-butylamino-ethyl)-sulphanilamide meltingat 76-78.

EXAMPLE 46 Analogously to Example 44(a), starting from 28.3 g. of N(2-cyclopenylamino-ethy1)-sulphanilamide, the hydrochloride of whichmelts at 190-191", and a solution of 11.9 g. of phenyl cyanate in 50 ml.of ether, l-sulphanilyl-2-imino 3 cyclopentyl-imidazolidine, M.P. 192193 is obtained.

The starting material is produced analogously to Example 45(b) from 32.5g. of N -(2-cyclopentylaminoethyl)-N -acetyl-sulphanilamide [cf. Example26(a)] and 300 ml. of ethanolic hydrochloric acid.

EXAMPLE 47 27.1 g. of 'N -(2-butylamino-ethyl)-sulphanilamide aredissolved in ml. of 2 N sodium hydroxide; 10.6 g. of cyanogen bromideare added thereto. Crystals precipitate. The reaction mixture is stirredat room temperature for one hour and then the crystals are filtered.Recrystallisation of the crude product from methanol yields pure 1sulphanilyl-2-imino-3-butyl-imidazolidine, M.P. l79-18l.

EXAMPLE 48 Analogously to Example 47, starting from 120 ml. of 2 Nsodium hydroxide solution, the following are obtained:

(a) With N (cyclopropylamino-ethyl) sulphanilamide and 10.6 g. ofcyanogen bromide, l-sulphanilyl-2- imino-3-cyclopropylimidazolidine,M.P. 202204; and

21 (b) With 28.3 g. of N -(cyclopentylamino-ethyl)-sulphanilamide and6.2 g. of cyanogen chloride,l-sulphamlyl-2-imino-3-cyclopentyl-imidazolidine, M.P. 192493.

EXAMPLE 49 A solution of 10.6 g. of cyanogen bromide in 50 ml. ofabsolute ether is added with stirring during 30 minutes at -10 to to asolution of 14.6 g. of butylamine in 100 ml. of absolute ether. Thereaction mixture is stirred 30 minutes longer and the precipitatedbutylaminehydrobromide is then removed by filtration. While cooling iscontinued, a suspension of 2.8 g. of sodium hydnde in 40 ml. of absoluteether is added to the filtrate, containing the resultant butyl-cyanamidedissolved therein. Cooling to the same temperature is continued whilethe suspension is stirred for another 30 minutes, and then 24.0 g. of4'-(aziridin-l-ylsulphonyl)-acetanilide is added to the resulting,suspended sodium derivative of the butylcyanamide. The mixture is warmedto room temperature and stirred for 15 hours at this temperature. 2 Nhydrochloric acid is then slowly added to the reaction mixture and thetwo phases which form are separated. The acidic aqueous phase is washedtwice with ether, purified with active charcoal, filtered and renderedalkaline at 0 with concentrated sodium hydroxide solution. The4-(2-imino- S-butyl-imidazolidin 1 ylsulphonyl)-acetanilide whichprecipitates is filtered and recrystallised from methanol; it then meltsat 243244.

The acetanilide which is obtained is hydrolysed analogously to Example9(b) to 1-sulphanilyl-2-imino-3-imin0- 3-butyl-imidazolidine, M.P.179-181 EXAMPLE 50 Analogously to Example 49, the following areobtained:

(a) From 6.2 g. of methylamine in 100' ml. of ether and 10.6 g. ofcyanogen bromide, the N-methyl-cyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thisyields with 24.0 g. of 4'-(aziridin-l-ylsulphonyl)-acetanilide, 4(2-imino-3-methyl-imidazolidin 1 ylsulphonyl)-acetan1- lide, M.P.266-267 which analogously to Example (b) is hydrolysed tol-sulphanilyl-2-imino-3-methyl-imidazolidine, M.P. 2092ll;

(b) From 9.0 g. of ethylamine in 100 ml. of ether and 10.6 g. ofcyanogen bromide, the N-ethyl-cyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thisyields with 24.0 g. of 4'-(aziridin-l-ylsulphonyl)-acetanilide, 4'-(2-imino 3 ethyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P. 267-269",which is hydrolysed according to Example 14 to1-sulphanilyl-2-imino-3-ethyl-imidazolidine;

(c) From 11.8 g. of propylamine in 100 ml. of ether and 10.6 g. ofcyanogen bromide, the propyl-cyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thisyields with 24.0 g. of 4'-(aziridin-l-yl-sulphonyl)-acetanilide, 4-(2-imino-3-propyl imidazolidin-l-ylsulphonyl) acetanilide, M.P. 253-255which is hydrolysed according to Example 8 to1-sulphanilyl-2-imino-3-propyl-imidazolidine, M.P. 164-166;

(d) From 14.6 g. of tert. butylamine in 100 ml. of ether and 10.6 g. ofcyanogen bromide, the tert. butylcyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to sodium derivative; thisyields with 24.0 g. of 4'-(aziridin-l-ylsulphonyl)-acetanilide, 4'-(2-imino-3-tert. butyl-imidazolidin-l-ylsulphonyl) -acetanilide, M.P.245-247, which is hydrolysed according to Example 20' to1-sulphanilyl-2-imino-3-tert. butyl-imidazolidine, M.P. 187-189";

(e) From 17.0 g. of cyclopentylamine in 100 ml. of ether and 10.6 g. ofcyanogen bromide, the cyclopentylcyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thisyields with 24.0 g. of 4'-aziridin-l-ylsulphonyl)-acetanilide, 4-(2-imino-3-cyclopentyl-imidazolidin-l-ylsulphonyl) acetanilide, M.P.261263, which is hydrolysed according to Example 26 to1-sulphanilyl-2-imino-3-cyclopentyl-imidazolidine, M.P. 192193; and

(f) From 19.8 g. of cyclohexylamine in ml. of ether and 10.6 g. ofcyanogen bromide, the cyclohexylcyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thisyields with 24.0 g. of 4'-(aziridin-l-ylsulphonyl)-acetanilide, 4(Z-imino 3 cyclohexyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P.283-284", which is hydrolysed according to Example 27 to1-sulphanilyl2-imino-3-cyclohexyl-imidazolidine, M.P. 178l79.

EXAMPLE 51 While stirring and cooling to 5 to 10, a solution of 14.6 g.of butylamine in 100 ml. of absolute ether is added dropwise to asolution of 10.6 g. of cyanogen bromide in 50 ml. of absolute ether.After several minutes the butylamine-hydrobromide precipitates. It isseparated by filtration. 2.8 g. of sodium hydride in 40 ml. of absoluteether are added in portions to the filtrate, in which thebutyl-cyanamide is dissolved. A precipitate forms. The suspension isdiluted with 200 ml. of absolute ether and 200 ml. of dioxane, and thenit is stirred for 10 minutes at room temperature. 19.8 g. ofl-sulphanilyl-aziridine are then added, the grey suspension is stirredfor 15 more hours and then 30 ml. of 2 N hydrochloric acid are added.The organic phase is separated and extracted twice with 2 N hydrochloricacid. The aqueous acidic phases are combined, purified with activecharcoal and filtered. The reaction mixture is neutralised with solidsodium hydrogen carbonate, whereby a brown resin precipitates. The resinis filtered over Celite (purified diatomaceous earth) and the clearcolourless solution is rendered alkaline with concentrated sodiumhydroxide solution. The reaction mixture is allowed to stand for onehour at 0, the precipitated crystals are filtered and recrystallizedfrom ethanol. 1-sulphanilyl-2-imino-3-butylimidazolidine, M.P. 179l8l,is obtained.

EXAMPLE 5 2 Analogously to Example 51, there are obtained:

(a) From 6.2 g. of methylamine in 100 ml. of ether and 10.6 g. ofcyanogen bromide, the methyl-cyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thiswith 19.8 g. of l-sulphanilyl-aziridine yields 1-sulphanilyl-2-imino-3-methyl-imidazolidine, M.P. 209-211";

(b) From 9.0 g. of ethylamine in 100 ml. of ether and 10.6 g. ofcyanogen bromide, the ethyl-cyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thiswith 19.8 g. of 1- sulphanilyl-aziridine yieldsl-sulphanilyl-2-imino-3-ethylimidazolidine, M.P. 17l172;

(c) From 11.8 g. of propylamine in 100 ml. of ether and 10.6 g. ofcyanogen bromide, the propyl-cyanamide, which with 2.8 g. of sodiumhydride in 40 m1. of ether is converted to the sodium derivative; thiswith 19.8 g. of l-sulphanilyl-aziridine yields 1-sulphanilyl-2-imino-3-propyl-imidazolidine, M.P. 164-166";

(d) From 14.6 g. of tert. butylamine in 100 ml. of ether and 10.6 g. ofcyanogen bromide, the tert. butylcyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thiswith 19.8 g. of l-sulphanilyl-aziridine yieldsl-sulphanilyl-2-imino-3-tert. butyl-imidazolidine, M.P. 187-189";

(e) From 17.0 g. of cyclopentylamine in 100 ml. of ether and 10.6 g. ofcyanogen bromide, the cyclopentylcyanamide, which 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thiswith 19.8 g. of l-sulphanilyl-aziridine yields Lsulphanilyl-Z-imino-3-cyclopentyl-irnidazolidine, M.P. 192-193; and

(f) From 19.8 g. of cyclohexylamine in 100 ml. of ether and 10.6 g. ofcyanogen bromide, the cyclohexylcyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thiswith 19.8 g. of 1-sulphanilyl-aziridine yields l-sulphanilyl-2-imino-3-cyclohexyl-imidazolidine, M.P. 178-179".

EXAMPLE 53 9.9 g. of l-tert. butyl-aziridine [cf. A. Weissberger,Heterocyclic Compounds With Three and Four-Membered Rings, John Wiley &Sons Inc., London (1964), p. 530] are dissolved in 60 ml. of dioxane andtreated with 10.6 g. of cyanogen bromide. In an exothermic reaction asolution of N-(2-bromo-ethyl)-N-tert. butylcyanamide is obtained, whichis added dropwise with stirring to a solution of 21.4 g. of4'-sulphamoyl-acetanilide in 100 ml. of 1 N sodium hydroxide solution.The reaction mixture is refluxed for one hour and then concentratedunder vacuum to half its volume. The crystals which precipitate arefiltered, washed with water, dried at 60" under vacuum andrecrystallised from ethyl acetate. The resulting 4'-(2-imino-3-tert.butyl-imidazolidinl-ylsulphonyl)-acetanilide melts at 245-247" and ishydrolysed according to Example 20 to yield 1-sulphanilyl2-irnino-3-tert. butyl-imidazolidine, M.P. 187-189".

EXAMPLE 5 4 Analogously to Example 53, the following are obtained:

(a) From 5.7 g. of l-methylaziridine and 10.6 g. of cyanogen bromide in60 ml. of dioxane, N-(Z-bromoethyl)-N-methyl-cyanamide, which with 21.4g. of 4'- sulphamoyl-acetanilide in 100 ml. of 1 N sodium hydroxidesolution yields4'-(2-imino-3-methyl-imidazolidinl-ylsulphonyl)-acetanilide, M.P.266-267"; this is hydrolysed according to Example (b) to l-sulphanilyl-2-imino-3-methyl-imidazolidine, M.P. 209-211";

(b) From 7.1 g. of l-ethyl-aziridine and 10.6 g. of cyanogen bromide in60 ml. of dioxane, N-(2-bromoethyl) N ethyl-cyanamide, which with 21.4g. of 4- sulphamolyl-acetanilide in 100 ml. of 1 N sodium hyide solutionyields 4-(2-imino-3-ethyl-imidazolidin-1-ylsulphonyl)-acetanilide, M.P.267-269"; this is hydrolysed according to Example 14 to1-sulphanilyl-2-imino-3-ethylimidazolidine, M.P. 171-172";

(c) From 8.5 g. of l-propyl-aziridine and 10.6 g. of cyanogen bromide in60 ml. of dioxane, N-(Z-bromoethyl)-N-propyl-cyanamide, which with 21.4g. of 4'- sulphamoyl-acetanilide in 100 ml. of 1 N sodium hydroxidesolution yields4-(2-imino-3-propyl-imidazolidinl-ylsulphonyl)-acetanilide, M.P.253-255"; this is hydrolysed according to Example 16 tol-sulphanilyl-Z-imino- 3-propyl-imidazolidine, M.P. 164-166".

(d) From 8.5 g. of 1-isopropyl-aziridine and 10.6 g. of cyanogen bromidein 60 ml. of dioxane, N-(Z-bromoethyl)-N-isopropyl-cyanamide, 'whichwith 21.4 g. of 4'- sulphamoyl-acetanilide in 100 m1. of 1 N sodiumhydroxide solution yields4'-(2-imino-3-isopropyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P.253-254"; this is hydrolysed according to Example 17 to 1-sulphani1yl-2-imino-3-isopropyl-imidazolidine, M.P. 183-184";

(e) From 9.9 g. of l-isobutyl-aziridine and 10.6 g. of cyanogen bromidein 60 ml. of dioxane, N-(2-bromoethyl)-N-isobutyl-cyanamide, which with21.4 g. of 4'- sulphamoyl-acetanilide in 100 ml. of 1 N sodium hydroxidesolution yields 4'-(2-imino-3-isobutyl-imidazolidin-1-ylsulphonyl)-acetanilide, M.P. 264-26-5; this is hydrolysed according toExample 18 to 1-sulphanilyl-2-imino- 3-isobutyl-imidazolidine, M.P.146-147";

(f) From 9.9 g. of l-sec. butyl-aziridine and 10.6 g. of cyanogenbromide in 60 ml. of dioxane, N-(2-bromoethyl)-N-sec. butyl-cyanamide,which with 21.4 g. of 4-sulphamoyl-acetanilide in 100 ml. of 1 N sodiumhydroxide solution yields 4'-(2-imino-3-sec.butyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P. 265-266"; this ishydrolysed according to Example 19 to l-sulphanilyl-Z- imino-3-sec.butyl-imidazolidine, M.P. 173-1735";

(g) From 11.3 g. of l-phenyl-aziridine and 10.6 g. of cyanogen bromidein 60 ml. of dioxane, N-(2-bromoethyl)-N-pentyl-cyanamide, which with21.4 g. of 4-sulphamoyl-acetanilide in 100 ml. of 1 N sodium hydroxide24 solution yields4-(2-imino-3-pentyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P.248-250"; this is hydrolysed according to Example 21 to l-sulphanilyl2-imino-3- pentyl-imidazolidine, M.P. 167-168" (h) From 12.7 g. ofl-hexyl-aziridine and 10.6 g. of cyanogen bromide in 60 ml. of dioxane,N-(Z-bromoethyl)-N-hexyl-cyanamide, which with 21.4 g. of4'-sulphamoyl-acetanilide in 100 ml. of 1 N sodium hydroxide solutionyields 4'-(2-imino-3-hexyl-imidaholidin-l-ylsulphonyl)-acetanilide, M.P.236-238"; this is hydrolysed according to Example 22 to1-sulphanilyl-2-imino-3-hexylimidazolidine, M.P. 182-183";

i) From 11.1 g. of l-cyclopentyl-aziridine and 10.6 g. of cyanogenbromide in 60 ml. of dioxane,N-(2-b1'omo-ethyl)-N-cyclopentyl-cyanamide, which with 21.4 g. of4'-sulphamoyl-acetanilide in 100 ml. of 1 N sodium hydroxide solutionyields 4' (Z-imino 3-cyclopentylimidazolidin-l-ylsulphonyl)-acetanilide,M.P. 261-263"; this is hydrolysed according to Example 26 to 1sulphanilyl-2 imino-3 cyclopentyl imidazolidine, M.P. 192-193"; and

(j) From 12.5 g. of l-cyclohexyl-aziridine and 10.6 g. of cyanogenbromide in 60 ml. of dioxane, N-(2-bromoethyl)-N-cyclohexyl-cyanamide,which with 21.4 g. of 4'-sulphamoyl-acetanilide in 100 ml. of 1 N sodiumhydroxide solution yields 4 (2 imino 3cyclohexylimidazolidin-l-ylsulphonyl)-acetanilide, M.P. 283-284"; thisis hydrolysed according to Example 27 to l-sulphanilyl-2 imino-3cyclohexyl imidazolidine, M.P. 178-179".

EXAMPLE 14.7 g. of 1-phenethyl-aziridine are dissolved in ml. of dioxaneand treated with 10.6 g. of cyanogen bromide. In an exothermic reactionN-(2-bromo-ethyl)-N-phenethyl-cyanamide is formed, which in the reactionsolution is added with stirring to a solution of 17.2 g. ofsulphanilamide in m1. of 1 N sodium hydroxide solution. The reactionmixture is refluxed for one hour and then concentrated under vacuum.Water is added to the residue, and the resulting precipitate is filteredand recrystallised from ethyl acetate. The resulting1-sulphanilyl-2-imino- 3-phenethyl-imidazolidine melts at 123-124".

EXAMPLE 56 Analogously to Example 55, the following are obtained:

(a) From 5.7 g. of l-methyl-aziridine and 10.6 g. of cyanogen bromide in60 ml. of dioxane, N-(2-bromoethyl) N methyl-cyanamide, which with 17.2g. of sulphanilamide in 100 ml. of 1 N sodium hydroxide solution yields1-sulphanilyl-2-imino-3-methyl-imidazolidine, M.P. 209-211 (b) From 7.1g. of l-ethyl-aziridine and 10.6 g. of cyanogen bromide in 60 ml. ofdioxane, N-(Z-bromoethyl) N-ethyl-cyanamide, which with 17.2 g. ofsulphanilamide in 100 ml. of 1 N sodium hydroxide solution yields1-sulphanilyl-2-imino-3-ethyl imidazolidine, M.P. 171-172";

(c) From 8.5 g. of l-propyl-aziridine and 10.6 g. of cyanogen bromide in60 ml. of dioxane, N-(2-bromoethyl) N propyl-cyanamide, which with 17.2g. of sulphanilamide in 100 ml. of 1 N sodium hydroxide solution yields1-sulphanilyl-2-imino-3-propyl imidazolidine, M.P. 164-166";

(d) From 8.5 g. of l-isopropyl-aziridine and 10.6 g. of cyanogen bromidein 60 ml. of dioxane, N-(2-bromoethyl) N-isopropyl-cyanamide, which with17.2 g. of sulphanilamide in 100 ml. of 1 N sodium hydroxide solu tionyields l-sulphanilyl-Z-imino 3 isopropyl-imidazolidine, M.P. 183-184";

(c) From 9.9 g. of l-butyl-aziridine and 10.6 g. of cyanogen bromide in60 ml. of dioxane, N-(2-bromoethyl)-N-butyl-cyanamide, which with 17.2g. of sulphanilamide in 100 ml. of 1 N sodium hydroxide solution yields1-sulphanilyl-2-imino-3-butyl imidazolidine, M.P. 179-181;

(f) From 9.9 g. of l-isobutyl-aziridine and 10.6 g. of cyanogen bromidein 60 m1. of dioxane, N-(Z-bromoethyl) N-isobutyl-cyanamide, which with17.2 g. of sulphanilamide in 100 ml. of 1 N sodium hydroxide solutionyields 1-sulphanilyl-2-imino-3-isobutyl-irnidazo1idine, M.P. 146147;

(g) From 9.9 g. of l-sec. butyl-aziridine and 10.6 g. of cyanogenbromide in 60 ml. of dioxane, N-(2-bromoethyl)-N-sec. butyl-cyanamide,which with 17.2 g. of sulphanilamide in 100 ml. of 1 N sodium hydroxidesolution yields 1-sulphanilyl-2-imino-3-sec. butyl-imidazolidine, M.P.173-1735";

(h) From 11.3 g. of l-phenyl-aziridine and 10.6 g. of cyanogen bromidein 60 ml. of dioxane, N-(2-bromoethyl) N pentyl-cyanamide, which with17.2 g. of sulphanilamide in 100 ml. of 1 N sodium hydroxide solutionyields 1-sulphanilyl-2-imino-3-pentyl-imidazolidine, M.P. 167-168;

(i) From 12.7 g. of l-hexyl-aziridine and 10.6 g. of cyanogen bromide in60 ml. of dioxane, N-(2-bromoethyl)-N-hexyl-cyanamide, which with 17.2g. of sulphanilamide in 100 ml. of 1 N sodium hydroxide solution yields1- sulphanilyl-2-imino-3-hexyl-imidazolidine, M.P. l82-183;

(j) From 11.1 g. of cyclopentyl-aziridine and 10.6 g. of cyanogenbromide in 60 ml. of dioxane, N-(2-bromoethyl)-N-cyclopentyl-cyanamide,which with 17.2 g. of sulphanilamide in 100 ml. of 1 N sodium hydroxidesolution yields 1-sulphanilyl-2-imino-3-cyclopentyl-imidazolidine, M.P.192-193"; and

(k) From 12.5 g. of l-cyclohexyl-aziridine and 10.6 g. of cyanogenbromide in 60 ml. of dioxane. N-(Z-bromo-ethyl) -N-cyclohexyl-cyanamide,which with 17.2 g. of sulphanilamide in 100 ml. of 1 N sodium hydroxidesolution yields 1 sulphanilyl 2 imino-3-cyclohexylimidazolidine, M.P.178-179".

EXAMPLE 5 7 A mixture of 16.0 g. of N-(2-chloro-ethyl)-N-tert.butyl-cyanamide, 5.6 g. of potassium hydroxide and 17.2 g. ofsulphanilamide in 100 ml. of diethylene glycol ether are heated for 30minutes in a bath having a temperature of 160-170". The reaction mixtureis then poured on to ice and the suspension is filtered. The filterresidue is dissolved in 2 N hydrochloric acid, the colour of thesolution is removed by active charcoal, the solution is filtered andrendered alkaline with concentrated sodium hydroxide solution. Thecrystals which precipitate are separated by filtration, Washed withwater and recrystallised from ethanol. l-sulphanilyl-2-imino-3-tert.butylimidazolidine, M.P. 188-190, is obtained.

EXAMPLE 5 8 (a) 34.6 g. of N -(2-bromo-ethyl)-N -cyano-N-acetylsulphanilamide are dissolved in 500 ml. of ethanol and 7.3 g. ofbutylamine, and refluxed for 17 hours. The reaction mixture isconcentrated and the residue is taken up in chloroform and 2 Nhydrochloric acid. The acidic aqueous extract is rendered alkaline withconcentrated sodium hydroxide solution. The crude product precipitates;it is separated by filtration and purified by recrystallisation fromethanol and acetone. The resulting 4'-(2-imino-3-butyl-imidazolidin-l-ylsulphonyl) acetanilide melts at 249-251". Thisacetanilide is hydrolysed according to Example 9(b) to1-sulphanilyl-2-imino-3-butyl-imidazo1idine, M.P. 179-181".

(b) The sulphanilamide used as starting material can be produced asfollows:

During 30 minutes a solution of 4.3 g. of aziridine in 20 ml. of etheris added dropwise at 0 to a solution of 10.6 g. of cyanogen bromide in30 ml. of ether. The resulting suspension is concentrated under vacuumat a bath temperature below 40. The residue is slurried in 60 ml.

of water, and a solution of 25 g. of N -acetyl-sulphanilyl chloride inml. of acetone is added to the resulting suspension. 4.5 g. of sodiumhydroxide in 10 ml. of water are then added dropwise thereto during 10minutes and the resulting mixture is refluxed for 30 minutes. Aftercooling, the crude product crystallises. It is separated by filtraation.Another yield of the crude product is obtained when the filtrate isdiluted with Water; it is separated and combined with the firstfraction. The two fractions are recrystallised from methanol to yield N-(2-bromo-ethyl)-N -cyano-N -acetyl-sulphanilamide melting at 177- 179.

EXAMPLE 59 Analogously to Example 58, starting from 34.6 g. of N(2-bromo-ethyl)-N -cyano-N -acetyl-sulphanilamide in 500 ml. of ethanol,the following are obtained:

(a) With 31.0 g. of methylamine,4-(2-imino-3-methyl-imidazolidin-l-ylsulphonyl) acetanilide, M.P. 266-267", which is hydrolysed according to Example 10(b) to1-sulphanilyl-2-imino-3-methyl-imidazolidine, M.P. 209-211;

(b) With 45.0 g. of ethylamine,4'-(2-imino-3-ethylimidazolidin-l-ylsulphonyl)-acetanilide, M.P.267-269", which is hydrolysed according to Example 14 tol-sulphanilyl-2-imino-3-ethyl-imidazolidine, M.P. 171-172";

(c) With 59.0 g. of propylamine,4-(2-imino-3-propylimidazolidin-l-ylsulphonyl)-acetanilide, M.P.253-255, which is hydrolysed according to Example 16 to l-sulphanilyl-2imino 3 propyl imidazolidine, M.P. 164- 166";

(d) With 59.0 g. of isopropylamine,4'-(2-imino-3-isopropyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P.253- 254", which is hydrolysed according to Example 17 to 1-sulphanilyl-2-imino-3-isopropyl-imidazolidine, M.P. 183- 184;

(e) With 73.0 g. of isobutylamine,4-(2-imino-3-isobutylimidazolidin-l-ylsulphonyl)-acetanilide, M.P. 264-265, which is hydrolysed according to Example 18 tolsulphanilyl-2-imino-3-isobutyl-imidazolidine, M.P. 146- 147;

(f) With 73.0 g. of sec. butylamine, 4'-(2-imino-3- sec.butyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P. 265-266, which ishydrolysed according to Example 19 to 1-sulphanilyl-2-imino-3-sec.butyl-irnidazolidine, M.P. 173173.5;

(g) With 73.0 g. of tert. butylamine, 4-(2-imino-3- tert.butyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P. 245-247", which ishydrolysed according to Example 20 to l-sulphanilyl-2-imino-3-tert.butyl-imidazolidine, M.P. 187-189;

(b) With 87.0 g. of pentylamine,4'-(2-imino-3-pentylimidazolidinl-ylsulphonyl -acetanilide, M .P. 248-250 which is hydrolysed according to Example 21 tol-sulphanilyl-2-imino-3-pentyl-imidazolidine, M.P. 167-168";

(i) With 85.0 g. of cyclopentylamine, 4-(2-imino-3-cyclopentyl-imidazolidin-l-ylsulphonyl)-acetanilide, M.P. 261-263, whichis hydrolysed according to Example 26 to1-sulphanilyl-2-imino-3-cyc1opentyl-imidazolidine, M.P. 192-193";

(j) With 99.0 g. of cyclohexylamine,4-(2-imino-3-cyclohexyl-imidazolidin-l-ylsulphonyl) acetanilide, M.P.283-284", Which is hydrolysed according to Example 27 to1-sulphanilyl-2-imino-3-cyclohexyl-imidazolidine, M.P. 178-179.

EXAMPLE 60 (a) A solution of 35.0 g. of N -(2-bromo-ethyl)-N cyano-N-acetyl-sulphanilamide and 10.0 g. of 3-methoxypropylamine in 250 ml. ofbutanol is refluxed for 1% hours. The mixture is then poured into aliter of ice water and extracted with methylene chloride. The aqueousphase is separated and he organic phase is extracted with 2 Nhydrochloric acid. The acidic aqueous extract is rendered alkaline withconcentrated sodium hydroxide solution. The crude product precipitates.It is filtered and recrystallised from acetone/ethanol, yielding4'-[2-imino-3- (3-methoxy-propyl)-imidazolidin-l ylsulphonyl]acetanilide, M.P. 233-235.

(b) 35.4 g. of the acetanilide obtained according to (a) are dissolvedin 150 ml. of 2 N hydrochloric acid and the solution is heated for onehour in a bath having a temperautre of 7880. The solution is then cooledand rendered alkaline with concentrated sodium hydroxide solution. Thecrude product precipitates. It is filtered and re crystallised fromethanol. The resulting l-sulphanilyl-Z-imino-3-(El-methoxy-propyl)-imidazolidine melts at 132 134.

EXAMPLE 61 (a) 38.9 g. of N -[2-N-isopropyl-benzylamino)-ethyl]- N-acetyl-sulphanilamide are dissolved in 500 ml. of benzene. 10.6 g. ofcyanogen bromide are added to the solution, the reaction mixture isstirred for 3 hours at room temperature and then concentrated. Theresidue is rendered alkaline with 2 N sodium hydroxide solution. Crystals precipitate which are washed with water and recrystallised frommethanol/ether. The resulting, pure 4-(2 imino 3 isopropyl imidazolidin1-ylsulphonyl)-acetanilide melts at 253. The acetanilide obtained ishydrolyzed according to Example 17 to1-sulphanilyl-2-imino-3-isopropyl-imidazolidine, M.P. 183184.

The starting material is produced as follows:

(b) 24.0 g. of 4-aziridin-l-ylsulphonyl)-acetanilide are dissolved in100 ml. of dioxane and 20 ml. of water, and, while stirring, arerefluxed for hours with 15.0 g. of N-benzyl-isopropylamine. The reactionmixture is then concentrated. The resulting oil crystallises in ethylacetate. Recrystallised from ethyl acetate, the pure N-[2-(N-isopropyl-benzylamino)-ethyl]-N acetyl sulphanilamide melts at8586.

EXAMPLE 62 (a) 37.45 g. of addition salt of N -cyano-N-acetylsulphanilamide and N-(2-chloro-ethyl)-tert. butylamine are heatedfor one hour in a bath having a temperature of 145, whereby the saltmelts. The reaction mixture is cooled, the resinous substance istriturated with 2 N hydrochloric acid, and the insoluble resin isseparated from the solution by decantation. The solution is renderedalkaline with concentrated sodium hydroxide solution, the crude productwhich precipitates is separated by filtration, washed with water andrecrystallised from ethanol. 4-(2-imino-3-tert. butyl imidazolidin 1ylsulphonyl)- acetanilide, M.P. 242-244, is obtained, which ishydrolysed according to Example to 1-sulphanilyl-2-imino-3- tert.butyl-imidadozidine, M.P. 187189.

The starting material is obtained as follows:

(b) To a solution of 8.6 g. of disodium cyanamide in 100 ml. of Water,there are added during 30 minutes in portions, 23.3 g. ofN-acetylsulphanilyl chloride, which gradually dissolves in a slightlyexothermic reaction. The solution is stirred for one hour at roomtemperature, whereby the sodium derivative of N -cyano-N-acetylsulphanilamide is formed. Then during 15 minutes, 17.2 g. ofN-(2-chloro-ethyl)-tert. butylarnine-hydrochloride are added in portionsto the reaction mixture. After an interval of a few minutes, theaddition salt of N -cyano-N acetyl-sulphanilamide andN-(2-chloro-ethyl)-tert. butylamine precipates. The salt is filtered,washed with water and recrystallised from isopropanol; it then melts at122-124".

EXAMPLE 63 (a) 15.5 g. of 1butyl-2imino-hexahydropyrimidine aredissolved in a solution of 4.8 g. of sodium hydroxide in 100 ml. ofwater. A solution of g. of N-acetyl-sulphanilyl chloride in 100 ml. ofacetone is added thereto. An exothermic reaction takes place andcrystals precipitate, The mixture is heated for 15 minutes longer in awater bath and then cooled to 0. The precipitated crystals are separatedby filtration and recrystallised from 28 ethanol. 4'-(2-imino-3-butylhexylhydropyrimidin-Z-ylsulphonyD-acetanilide, M.P. 189191, is obtained.

(b) 35.2 g. of the acetanilide obtained according to (a) are dissolvedin 180 ml. of 8 N ethanol hydrochloric acid, and this solution isallowed to stand for 2 days at room temperature. The reaction mixture isconcentrated and the residue is dissolved in water. The solution isseparated by filtration and rendered alkaline with sodium hydroxidesolution. The crystals which precicitate are separated by filtration,washed with water and recrystallised from acetone/methanol, to yield1-sulphanilyl-2- imino-3-butyl-hexahydropyrimidine melting at 180-183".

EXAMPLE 64 The following are produced analogously to Example 63(a):

(a) From 23.4 g. of 1-octyl-2-amino-2-imidazoline hydrochloride and 12.0g. of sodium hydroxide in 120 ml. of water with 15.0 g. ofN-acetyl-sulphanilyl chloride, which has been dissolved in 150 ml. ofwarm acetone, 4'- (2-imino-3-octyl-imidazolidin-l-ylsulphonyl)acetanilide, M.P. 229230, which is hydrolysed analogously to Example 63(b) to 1-sulphanilyl-2-imino-3-octyl-imidazolidine, M.P. 143-144";

(b) From 26.2 g. of 1-decyl-2-amino-2-irnidazoline hydrochloride and12.0 g. of sodium hydroxide in 120 ml. of water with 15.0 g. ofN-acetyl-sulphanilyl chloride, which has been dissolved in 150 ml. ofwarm acetone, 4- (2-imino-3-decyl-imidazolidin 1 ylsulphonyl)acetanilide, M.P. 216-217, which is hydrolysed analogously to Example 63(b) to 1-sulphanilyl-2-imino-3-decyl-imidazolidine, M.P. 119-120;

(c) from 29.0 g. of 1-dodecyl-2-amino-2-imidazoline hydrochloride and12.0 g. of sodium hydroxide in 120 ml. of water with 15 .0 g. ofN-acetyl-sulphanilyl chloride, which has been dissolved in 150 ml. ofwarm acetone, 4'-(2-imino-3-dodecyl imidazolidin-l-ylsulphonyl)-acetanilide, M.P. 218219, which is hydrolysed analogously to Example 63 (b)to 1-sulphanilyl-2-imino-3-dodecyl-imidazolidine, M.P. -1 1 1 (d) From22.6 g. of 1-phenethyl-2-amino-2-imidazoline hydrochloride and 12.0 g.of sodium hydroxide in ml. of water with 15.0 g. of N-acetyl-sulphanilylchloride, which has been dissolved in ml. of Warm acetone,4'-(2-imino-3-phenethyl imidazolidin-l-ylsulphonyl)-acetanilide (crudeproduct), which is hydrolysed analogously to Example 63(b) to1-sulphanilyl-2-imino-3- phenethyl-imidazolidine, M.P. 123124;

(e) From 21.2 g. of 1-benzyl-2-amino-2-imidazoline hydrochloride and12.0 g. of sodium hydroxide in 120 ml. of water with 15.0 g. ofN-acetyl-sulphanilyl chloride, which has been dissolved in 150 ml. ofwarm acetone, 4'-(2-irnino-3-benzyl imidazolidin-1-ylsulphonyl)acetanilide, M.P. 268-269, which is hydrolysed analogously to Example 63(b) to 1-sulphanilyl-2-imino-3-benzyl-imidazolidine. M.P. -171; and

(f) From 25.6 g. of 1-(l-adamantyl)-2-amino-2-imidazoline hydrochlorideand 12.0 g. of sodium hydroxide in 120 ml. of water with 15.0 g. ofN-acetyl-sulphanilyl chloride, which has been dissolved in 150 ml. ofwarm acetone, 4'-[2-im-ino-3-(l-adamantyl)imidazolidin-l-ylsulphonyl]-acetanilide, M.P. 273-275 which ishydrolysed analogously to Example 63(b) to 1-sulphanilyl-2imino-3-(l-adamantyl)-imidazolidine, M.P. 240243.

EXAMPLE 65 13.2 g. of cyanogen bromide in 220 ml. of ether are added to31.0 g. of crude N-tert. butyl-1,2-propanediamine-dihydrobromide. During5 minutes, a solution of 11.4 g. of sodium carbonate in 88 ml. of wateris added in portions to the resulting mixture. The suspension obtainedis stirred for 15 hours at room temperature and allowed to stand for 2days. The aqueous layer, containing l-tert.butyl-2-amino-4-methyl-2-imidazoline, is separated from the ethersolution and the aqueous phase is diluted with water to dissolve theprecipitated sodium bromide. To the aqueous solution, a solution of 23.8g. of N-acetyl-sulphanilyl chloride in 220 ml. of acetone is added andalso a solution of 8.8 g. of sodium hydroxide in 44 ml. of water. Themixture is then refluxed for 30 minutes, cooled; the crude product whichprecipitates is separated by filtration and recrystallisedfromchloroform/ ethanol. 4-(2-imino-3-tert.butyl-S-methyl-imidazolidin-1- ylsulphonyl)-actanilide, M.P. 238-240, isobtained.

(b) The acetanilide obtained according to (a) is hydrolysed analogouslyto Example 63 (b) to l-sulphanilyl- 2-imino-3-tert.buty1-5-methyl-imidazolidine, M.P. 145- 146.

The starting product for (a) can be produced as follows:

(c) 16.35 g. of N-tert. butyl-2-chloro-propionamide [cf. J. Am. Chem.Soc., 78, 6124 (1956)] and 25.0 g. of benzylamine are heated at a bathtemperature of 150- 170 for 3% hours. From the solution which isoriginally homogeneous, crystals precipitate. The reaction mixture iscooled and 150 ml. of 2 N sodium hydroxide solution and chloroform areadded thereto. The organic phase is separated, washed with water, driedand concentrated. The residue is distilled. After a first running ofbenzylamine, N-tert. butyl-(2-benzylamine)-propionamide, B.P.123-125/0.03 torr, is obtained. The hydrochloride melts at 158-162.

(d) A solution of 23.4 g. of the amide obtained according to (c) in 80ml. of absolute tetrahydrofuran is added dropwise during 15 minutes to asuspension of 9.0 g. of lithium aluminium hydride in 200 ml. of absolutetetrahydrofuran. The suspension is then refluxed for 38 hours. Thecolour changes to raspberry red and during a period of 30 minutes backto grey again. The reaction mixture is cooled, the excess lithiumaluminium hydride is decomposed, while cooling, with ethyl acetate, thenwith water and with methanol and the suspension is concentrated. Thegrey residue is extracted twice with boiling chloroform during 30minutes and filtered. The combined chloroform solutions are dried oversodium sulphate and concentrated. The residual oil is distilled. N-tert.butyl- N-benzyl-1,2'propane-diamine distills at 72-86/ 0.005 torr.

(e) 34.0 g. of 48% pure hydrogen bromide and 8.8 g. of palladiumcharcoal are added to 22.0 g. of the amine obtained according to (d) in440 ml. of distilled ethanol. The mixture is hydrogenated at roomtemperature and normal pressure. After 95% of the calculated amount ofhydrogen has been taken up, 8.8 g. of 5% palladium charcoal are addedand hydrogenation is continued. After 17 hours, the reaction mixture hastaken up 98% of the calculated amount of hydrogen. The catalyst isremoved by filtration, rinsed with ethanol, and the filtrate isconcentrated. The residue, N-tert. butyl- 1,2-propanediamine'dihydrobromide, is used as crude product.

EXAMPLE 66 (a) Analogously to Example 65 (a-b), the following endproduct is obtained:

From N-butyl-1,2-propanediamine and cyanogen bromide, 1butyl-2-amino-4-methyl-2-imidazoline hydrobromide (crude product), whichwith N-acetyl-sulphanilyl chloride yields4'-(2-imino-3-butyl-5-methyl-imidazolidinl-ylsulphonyl)-acetanilide,M.P. 243-244", the hydrolysis of which yields l-sulphanilyl-Z-amino 2butyl 5- methyl-imidazolidine, M.P. 125-126.

The starting material is obtained as follows:

(b) While cooling well with ice, 12.7 g. of 2-chloropropionyl chloridein 20 ml. of chloroform are added dropwise during 30 minutes to asolution of 16.1 g. of butylamine in 50 ml. of chloroform. The resultingsolution is allowed to stand for hours at room temperature,

then washed several times with water, and the organic phase isseparated. The organic phase is dried over sodium sulphate andconcentrated. Crude N-butyl-Z-chloro-propionamide remains as residue.

(c) Analogously to Example 65(c-e), starting from the crude amide from(b) via the intermediate products N-butyl-Z-benzenylamino propionamide,B.P. 151-154/ 0.0005 torr and N-butyl-N-benzyl-1,2-propanediamine, B.P.98-104/0.04 torr, N-butyl-1,2-propanediamine is obtained.

EXAMPLE 67 (a) Analogously to Example 65 (a-b), the following endproduct is obtained:

From N-butyl-1,2-butanediamine (crude product) and cyanogen bromide,1-butyl-2-amino-4-ethyl-2-imidazolidinexiihydrobromide (crude product),which with N- acetyl-sulphanilyl chloride yields 4'-(2-imino-3-butyl-5ethyl-imidizolidin-l-ylsulphonyl)-acetanilide (crude product), M.P.107-111, which is hydrolysed to l-sulphanilyl-2-imino-3-butyl-5-ethyl-imidazolidine, M.P. 161-163 The startingmaterial for (a) is produced as follows:

(b) Analogously to Examples 66(b) and 65(c-e), starting from2-chloro-butyryl chloride via the intermediate products N-butyl 2-chlorobutyramide (crude product) N-butyl-Z-benzylamino-butyramide(crude product) and N butyl-N-benzyl-l,Z-butanediamine (crude product),N-butyl-1,2-butanediamine is obtained.

EXAMPLE 68 Analogously to Example 63(a) the following end products areobtained:

(a) From 24.0 g. of I-(Z-methyIthio-ethyl)-2-amino- Z-imidazolinehydrobromide (M.P. 138-140") and 12.0 g. of sodium hydroxide in ml. ofwater with 23.3 g. of N-acetyl-sulphanilyl chloride, which has beendissolved in ml. of warm acetone,4-[2-imino-3-(2-methylthioethyl)-imidazolidin-l-ylsulphonyl]acetanilide,M.P. 257- 259", which is hydrolysed analogously to Example 63 (b) tol-sulphanilyl-2-imino-3-(Z-methylthio ethyl) imidazolidine, M.P.152-153".

The starting material is produced analogously to Example 65 (a) from13.4 g. of N-(Z-amino-ethyl)-2-methylthio-ethylamine and 10.6 g. ofcyanogen bromide;

(b) From 22.4 g. of 1-(2-methoxy-ethyl)-2-amino-2- imidazolinehydrobromide (M.P. 141-144) and 12.0 g. of sodium hydroxide in 120 ml.of water with 23.3 g. of N-acetyl-sulphanilyl chloride, which has beendissolved in 150 ml. of warm acetone 4-[2-imino-3-(2-methoxyethyl)-imidazolidin 1 ylsulphonyl] acetanilide, M.P. 230-232", which ishydrolysed analogously to Example 63 (b) to l-sulphanilyl 2 imino 3-(2methoxy-ethyl)- imidazolidine, M.P. 230-232".

The starting material is produced analogously to Example 65 (a) from23.8 g. of N (2-amino-ethyl) 3- methoxy-ethylamine and 10.6 g. ofcyanogen bromide;

(c) From 23.8 g. of 1-(3-methoxy-propyl)-2-amino2- imidazolinehydrobromide (crude product) and 12.0 g. of sodium hydroxde in 120 ml.of water with 23.3 g. of N-acetyl-sulphanilyl chloride, which has beendissolved in 150 ml. of warm acetone, 4-[2-imino-3-(3-ethoxypropyl)imidazolidin 1 ylsulphonyl] acetanilide, M P 230-232, which ishydrolysed analogously to Example 63 (b) to 1-sulphanilyl-2-imino-3-(3methoxy propyl)- imidazolidine, M.P. 132-134.

The starting material is produced analogously to Example 65(a) from 23.8g. of N (2 amino ethyl) 3- methoxy-propylamine and 10.6 g. of cyanogenbromide;

(d) From 25.2 g. of 1-(3-ethoxy-propyl)-2-amino-2- imidazolinehydrobromide (crude product) and 12.0 g. of sodium hydroxide in 120 ml.of water with 23.3 g. of N-acetyl-sulphanilyl chloride, which has beendissolved in 150 ml. of warm acetone, 4 [2 imino 3 (3 ethoxypropyl)imidazolidin 1 ylsulphonyl1acetanilide, M.P. 220-223, which ishydrolysed analogously to Example 31 63 (b) to 1 sulphanilyl 2imino-3-(3-ethoxy-propyl)- imidazolidine, M.P. 148-150.

The starting material is produced analogously to Example 65(a) from 14.6g. of N-(2-amino-ethyl)3-ethoxypropylamine and 10.6 g. of cyanogenbromide;

(c) From 26.6 g. of l-(3-isopropoxy-propyl)-2-amino- 2-imidazolinehydrobromide (crude product) and 12.0 g. of sodium hydroxide in 120 ml.of water with 23.3 g. of N-acetylsulphanilyl chloride, which has beendissolved in 150 ml. of warm acetone, 4-[2-imino3-(3-isopropoxy-propyl)-imidazolidin 1 ylsulphonyl1-acetanilide, M.P.224-226, which is hydrolysed analogously to Example 63(b) to1-sulphanilyl-2-imino-3-(3-isopropoxy-propyl)-imidazolidine, M.P.133-135".

The starting material is produced analogously to Ex ample 65(a) from16.0 g. of N-(2-amino-ethyl)-3-isopropoxy-propylamine and 10.6 g. ofcyanogen bromide; and

(f) From 28.0 g. of 1-(3-but0xy-propyl)-2-amino-2- imidazolinehydrobromide (crude product) and 12.0 g. of sodium hydroxide in 120 ml.of water with 23.3 g. of N-acetyl-sulphanilyl chloride, which has beendissolved in 150 ml. of Warm acetone,4'-[2-imino-3-(3-butoxypropyl)-imidazolidin 1 ylsulphonyl]-acetanilide,M.P. 210-212, which is hydrolysed analogously to Example 63(b) tol-sulphanilyl 2 imino-3-(3-butoxy-propyl)- imidazolidine, M.P. 126-128".

The starting material is produced analogously to Example 65(a) from 17.4g. of N-(Z-amino-ethyl)-3-butoxypropylamine and 10.6 g. of cyanogenbromide.

EXAMPLE 69 (a) Analogously to Example 9(a), starting from 30.1 g. of N(2 cyclohexylamino-ethyl)-p-nitro-benzenesulphonamide (crude product)and 10.6 g. of cyanogen bromide in 100 ml. of 2 N sodium hydroxidesolution, 1-(p-nitro-phenylsulphonyl) 2imino-3-cyclohexyl-imidazolidine, M.P. 98-99 (from benzene) is obtained.

(b) 35.2 g. of the nitro compound produced according to (a) aredissolved in one liter of ethanol, and, in the presence ofpalladium-charcoal (50% palladium), then hydrogenated at 20 and normalpressure until cessation of the reaction. The catalyst is then removedby filtration, rinsed with ethanol, and the filtrate is concentratedunder vacuum. Recrystallisation of the residue from dioxane/water yieldspure l-sulphanilyl-Z-imino-3- cyclohexyl-imidazolidine, M.P. 181-183 Thestarting material used for (a) is obtained analogously to Example 9(c)from 22.8 g. of l-(p-nitrophenylsulphonyl)-aziridine and 150 ml. ofcyclohexylamine.

EXAMPLE 70 (a) 25.6 g. of N-(2-propylamino-ethyl)-p-toluenesulphonamideare dissolved in 100 ml. of 2 N sodium hydroxide solution and, whilecooling at 20-30, 10.6 g. of cyanogen bromide are added. The reactionmixture is allowed to stand for 10 minutes and the crystals which haveprecipitated are then filtered. The crude product is recrystallised fromethyl acetate to yield l-(p-tolylsulphonyl) 2 imino 3propyl-irnidazolidine melting at 95-96".

The starting material is produced as follows:

(b) A solution of 190.5 g. of p-toluenesulphonyl chlo ride and 250 ml.of acetone is added dropwise during 20 minutes with stirring to asolution of 43.0 g. of aziridine in 300 ml. of 4 N sodium hydroxidesolution which has been cooled to l0. The reaction mixture is stirredfor 2 hours at 0-10 with cooling. 2 liters of Water are then added tothe mixture and it is extracted three times with 500 ml. of ether. Theether extract is dried over Sodium sulphate and concentrated undervacuum. The residue, crude 1-(ptolylsulphonyl)-aziridine, melts at 54-56".

(c) A solution of 19.7 g. of l-(p-toylsulphonyl)-aziridine in 100 ml. ofdioxane and ml. of water is added dropwise at room temperature to ml. ofpropylamine, and the reaction mixture is refluxed for one hour. It isthen concentrated under vacuum. Recrystallisation of the residue fromethyl acetate/ petroleum ether yields pure N-(2-propylamino-ethyl)p-toluene-sulphonamide, M.P. 39-41.

EXAMPLE 71 Analogously to Example 70(a), starting from 10.6 g. ofcyanogen bromide, the following end products are obtained:

(a) With 27.0 g. of N-(2-tert. butylamino-ethyl)-ptoluene-sulphonamide,M.P. 67-68 (from ethyl acetate/ ether), 1(p-tolylsulphonyl)-2-imino-3tert. butyl-imidazolidine, M.P. -131 [thestarting product is produced analogously to Example 70(c) from 19.7 g.of l-(p-tolylsulphonyl)-aziridine and 100 ml. of tert. butylamine]; and

(b) With 29.6 g. of N-(2-cyclohexylamino-ethyl)-ptoluene-sulphonamide,M.P. 65-66" (from ethyl), l-(ptolylsulphonyl)-2-imino 3cyclohexyl-imidazolidine, M.P. 118-120 [the starting product is producedanalogously to Example 70(c) from 19.7 g. ofl-(tolylsulphonyl)-aziridine and 100 ml. of cyclohexylamine].

EXAMPLE 72 (a) A solution of 11.2 g. of cyanogen bromide in 120 ml. ofether is added during 10 minutes at room temperature to a'solution of35.0 g. of N-[2-(1-adamantylamino)-ethyl]-p-toluenesulphonamide in 175ml. of dioxane. The resulting suspension is refluxed for 90 minutes at abath temperature of 70. The reaction mixture is then concentrated andthe oily residue is taken up in 2 N sodium hydroxide solution andmethylene chloride. The organic phase is washed with water, dried oversodium sulphate and concentrated. The residue which is partiallycrystalline is purified by elution chromatography on 5 80 g. of silicagel. The 1-(p-tolylsulphonyl-2-imino-3-(l-adamantyl)-imidazolidine iseluted with chloroform/ethanol (100:1); after recrystallisation frommethanol/methylene chloride it melts at 187-189. The chloroform/ etherfraction (1:1) contains unchanged starting material.

(b) A solution of 19.7 g. of 1-(p-tolylsulphonyl)- aziridine is addedduring 30 minutes with stirring at 80 to a solution of 15.1 g. ofl-amino-adamantane in 35 ml. of dioxane. After completion of theaddition, the reaction solution is stirred 90 minutes longer at a bathtemperature of 80. The reaction mixture is then concentrated and theresidue is purified by elution chromatography on a column of 500 g. ofsilica gel. N-[2- (1-adamantylamino)-ethyl]-p-toluenesulphonamide isobtained from the chloroform/ethanol fractions (9:1) and (4:1). Thefinal product is recrystallised from methanol; it then melts at117-120".

EXAMPLE 73 Analogously to Example 72(a) the following end products areobtained from cyanogen bromide:

(a) With N [2-(l-homoadamantylamino)-ethyl]-ptoluenesulphonamide, M.P.101-103 (from methanol, hygroscopic),l-(p-tolylsulphonyl)-2-imino-3-(1-homoadamantyl)-imdazolidine, M.P. -172[the starting product is produced analogously to Example 72(b) from1-(p-tolylsulphonyl)-aziridine and l-amino-homoadamantane]; and

(b) With N-[Z-(octahydro-l,2,4-methenopentalen-5-ylamino)-ethyl]-p-toluenesulphonamide, M.P. 113-115 (from methanol),l-(p-tolylsulphonyl)-2-imino-3-(octahydro-1,2,4-methenopentalen-5-yl)-imidazolidine,M.P. 123- 124 [the starting product is produced analogously to Example72(b) from l-(p-tolylsulphonyl)-aziridine and 5-amino-octahydro-1,2,4-methenopentalene] EXAMPLE 74 (a) 24.4 g. ofN-(Z-methylamino-ethyl)-p-methoxybenzenesulphonamide are dissolved in100 ml. of 2 N sodium hydroxide solution and while cooling at 20-30,10.6 g. of cyanogen bromide are added thereto. The reaction mixture isallowed to stand for 3 hours and then the crystals which haveprecipitated are filtered. The crude product is recrystallised frommethanol to obtain l-(pmethoxy-phenylsulphonyl)2-imino-3-methyl-imidazolidine melting at l04107.

The starting material is produced as follows:

(b) A solution of 20.6 g. of p-methoxy-benzenesulphonyl chloride in 250ml. of acetone is added dro-pwise during 20 minutes with stirring to asolution of 4.3 g. of aziridine in 300 ml. of 4 N sodium hydroxidesolution which has been cooled to The reaction mixture is stirred for 2hours at 0-10 with cooling. Then 2 liters of water are added to themixture and it is extracted three times with 500 ml. of ether. The etherextract is dried over sodium sulphate and concentrated under vacuum. Theresidue, 1-(p-methoxy-phenylsulphonyl)-aziridine, melts at 45-46 (fromethyl-acetate/ petroleum ether).

(c) A solution of 21.3 g. of l-(p-methoxy-phenylsulphonyl)-aziridine in100 ml. of dioxane and ml. of water is added dropwise at roomtemperature to 300 ml. of 33% methylamine in ethanol, and the reactionmixture is refluxed for one hour. It is then concentrated under vacuum.The residue is purified by elution chromatography on silica gel. Fromthe chloroform/ethanol fraction (9:1)N-(Z-methylamino-ethyl)-p-methoxy-benzenesulphonamide is obtained, whichmelts at 68-69 after recrystallisation from ethyl acetate.

EXAMPLE 75 Analogously to Example 74(a), starting from 10.6 g. ofcyanogen bromide, the following end products are obtained:

(a) With 28.6 g. ofN-(Z-butyIamino-ethyl)-p-methoxy-benzenesulphonamide, M.P. 66-68 (fromether), 1- (p-methoxy-phenylsulphonyl) 2-imino-3-butyl-imidazolidine,M.P. 85-86 [the starting material is produced analogously to Example74(e) from 21.3 g. ofl-(pmethoxy-phenylshlphonyl)-aziridine and 500 ml.of butylamine); and

(b) With 28.6 g. of N-(Z-tert. butylamino-ethyl)-pmethoxybenzenesulphonamide, M.P. 97-99 (from ether),1-(p-methoxy-phenylsulphonyl)-2-imino 3 tert. butyl-imidazolidine, M.P.107-108" (from methanol) [the starting product is produced analogouslyto Example 74(e) from 21.3 g. of 1-(p-methoxy-phenylsulphonyl)-aziridine and 500 ml. of tert. butylamine].

EXAMPLE 76 Analogously to Example 74(a), starting from 10.6 g. ofcyanogen bromide, the following end product is obtained:

(a) With 28.8 g. ofN-(Z-propylamino-ethyl)-p-methylthio-benzenesulphonamide, M.P. 79-8l(from ethyl acetate), 1-(p-methylthio-phenylsulphonyl) 2 imino-3-propyl-imidazolidine.

(b) The starting material for (a) is produced as follows:

Analogously to Example 74(b), 22.3 g. of p-methylthio-benzenesulphonylchloride and 4.3 g. of aziridine yield1-(p-methylthio-phenylsulphonyl)-aziridine (crude product); 22.9 g. ofthe latter are converted analogously to Example 74(e) with 500 ml. ofpropylamine to 1- (2-propylamino-ethy1) pmethylthio-benzenesulphonamide.

EXAMPLE 77 Analogously ot Example 70(a), starting from 10.6 g. ofcyanogen bromide, the following end products are obtained:

(a) With 30.2 g. ofN-(Z-butylamino-ethyl)-p-methylthio-benzenesulphonamide, M.P. 88-89(from ether), 1- (p-methylthio-phenylsulphonyl) 2 imino-3-butyl-im- 34idazolidine, M.P. 87-88 (from ether) [the starting material is producedanalogously to Example 70(c) from 22.9 g. of1-(p-methylthio-phenylsulphonyl)-aziridine and 500 ml. of butylamine]and (b) With 30.2 g. of N-(2-tert.butylamino-ethyl)-pmethylthio-phenylsulphonamide (crude product),l-(pmethylthio-phenylsulphonyl) 2 imino-3-tert. butyl-imidazolidine,M.P. l 38-13-9 (from ethyl acetate) [the starting material is producedanalogously to Example 70(c) from 22.9 g. of1-(p-methylthio-phenylsulphonyl)-aziri1 dine and 500 ml. of tert.butylamine].

In addition, analogously to Example 74(a), starting from 10.6 g. ofcyanogen bromide, the following end product is obtained:

(c) With 32.8 g. ofN-(2-cyclohexylaminoethyl)-pmethylthio-benzenesulphonamide, M.P.131-132" (from methanol) 1- (p-methylthio-phenylsulphonyl -2-imino-3-cyclohexyl-imidazolidine, M.P. 129-130 (from ethyl acetate) [thestarting material is produced analogously to Example 74(0) from 22.9 g.of l-(p-methylthio-phenylsulphonyl)-aziridine and 300 ml. ofcyclohexylamine.

EXAMPLE 78 Analogously to Example 70(a), starting from 10.6 g. ofcyanogen bromide, the following is obtained:

(a) With 27.6 g. of N-(2-propylamino-ethyl)-p-chloro-benzenesulphonamide(crude product), l-(p-chlorophenylsulphonyl)2-imino-3-propyl-imidazolidine. This end product is purified by elutionchromatography on silica gel, being eluted with chloroform/ethanol(9:1), M.P. 68-69".

(b) The starting material is obtained by starting fromp-chloro-phenylsulphonyl chloride, which with aziridine, analogously toExample 70(b), yields l-(p-chloro-phenylsulphonyl)-aziridine (crudeproduct); 21.7 g. of this aziridine are converted with 300 ml. ofpropylamine analogously to Example 70(c) toN-(Z-propylamino-ethyl)-pchloro-benzenesulphonamide.

EXAMPLE 79 Analogously to Example 70(a), starting from 10.6 g. ofcyanogen bromide, the following end products are obtained:

(a) With 29.0 g. of N-(Z-butylamino-ethyl)-p-chlorobenzenesulphonamide(crude product), l-(p-chloro-phenylsulphonyl) 2 imino 3 butylimidazolidine, M.P. 74-75" [the starting material is producedanalogously to Example 70(c) from 21.7 g. ofl-(p-chloro-phenylsulphonyl)-aziridine and 300 ml. of butylamine]; and

(b) With 31.6 g. ofN-(2-cyclohexylamino-ethyl)-pchlorobenzenesulphonamide, M.P. 83-84 (fromethylacetate/ether), l (p chloro-phenylsulphonyl)-2-imino-3-eyclohexyl-imidaz-olidine, M.P. 108-110 [the starting material isproduced analogously to Example 70(0) from 21.7 g. of1-(p-chloro-phenylsulphonyl)-aziridine and 300 ml. of cyclohexylamine].

EXAMPLE (b) With 24.2 g. of N-(2-isopropylamino-ethyl)-ben-'zenesulphonamide, M.P. 59-60 (from ethyl acetate), 1- phenylsulphonyl 2imino 3 isopropyl-imidazolidine,' M.P. 71-72 (from ethyl acetate/ether)[the starting material is produced analogously to Example 70(c) from18.3 g. of 1-phenylsulphonyl-aziridine and 300 ml. of

isopropylamine] (c) With 25.6 g. of N(2-butylamino-ethyl)-benzenesulphonamide, M.P. 56-57 (from ether),l-phenylsulphonyl 2 imino 3 butyl imidazolidine, M.P. 84- 85 (fromether) [the starting material is produced analogously to Example 1(c)from 18.3 g. of l-phenylsulphonyl-aziridine and 300 ml. of butylamine];

(d) With 25.6 g. of N-(Z-tert. butylamino-ethyl)-benzenesulphonamide,M.P. 8990 (from ethyl acetate), 1- phenylsulphonyl 2 imino-3 tert.butyl-imidazolidine, M.P. 98-100 (from ethyl acetate/ether) [thestarting material is produced analogously to Example 70(c) from 18.3 g.of 1-phenylsulphonylaziridine and 300 ml. tert. butylamine]; and

(e) With 28.2 of N-(2-cycloxylamino-ethyl)-benzenesulphonamide, M.P.79-80 (from ethyl acetate),l-phenylsulphonyl-2-imino-3-cyclohexyl-imidazolidine, M.P. 94 95 (fromethyl acetate/ether) [the starting material is produced analogously toExample 70(c) from 18.3 g. of 1-phenylsulphonylaziridine and 300 ml. ofcyclohexylamine].

EXAMPLE 81 Analogously to Example 70(a), starting from 10.6 g. ofcyanogen bromide, the following end product is obtained:

(a) With 29.8 g. of N-(Z-tert.butylamino-ethy1)-pacetyl-benzenesulphonamide, M.P. 116-117 (fromisopropanol), 1 (p acetyl-phenylsulphonyl-2-imino-3-tert.butyl-imidazolidine, M.P. 144-146 (from isopropanol).

(b) The starting product for (a) is produced starting fromp-acetyl-benzenesulphonyl chloride, which with aziridine analogously toExample 70(b) yields '1-(pacetyl-phenylsulphonyl)-aziridine (crudeproduct). 22.5 g. of this aziridine are converted analogously to Example70(c) with 300 m1. of tert. butyl-amine to N-(tert.butylamino-ethyl)-p-acetyl-sulphonamide.

EXAMPLE 82 Analogously to Example 70(a), starting from 10.6 g. ofcyanogen bromide, the following end products are obtained:

(a) With 29.8 g. of N-(Z-butylamino-ethyl)-p-acetylbenzenesulphonamide,M.P. 8990 (from isopropanol), 1 (pacetyl-phenylsulphonyl)-2-imino-3-butyl-imidazolidine, M.P. 120-122(from isopropanol) [the starting material is produced analogously toExample 70(c) from 22.5 g. of 1-(p-acetyl-phenylsu1phonyl)-aziridine and300 ml. of butylamine]; and

(b) With 40.7 g. of N-(2-cyclohexylarnino-ethyl)-p- (lcyclohexylimino-ethyl)-benzenesulphonamide, M.P. 85-86 (fromisopropanol), 1-(p-acetyl-phenylsulphonyl- 2 imino 3cyclohexyl-imidazolidine, M.P. 164-166 (from isopropanol) [the startingproduct is produced analogously to Example 70(c) from 22.5 g. ofl-(p-acetylphenylsulphonyl)-aziridine and 300 ml. of cyclohexylamine].

EXAMPLE 83 Analogously to Example 70(a) starting from 10.6 g. ofcyanogen bromide, the following end product is obtained:

(a) With 27.4 g. of N-(Z-butylamino-ethyl)-p-fluorobenzenesulphonamide(crude product), l-(p-fluoro-phenylsulphonyl) 2 imino 3butyl-imidazolidine, M.P. 74-76.

(b) The starting material for (a) can be produced starting fromp-fluoro-benzenesulphonyl chloride, which, analogously to Example 70(b),is converted with aziridine to 1-(p-fluorophenylsulphonyl)-aziridine,20.1 g. of which with 150 ml. of butylamine yield, analogously toExample 70(c), N (2-butylaminoethyl)-p-fluoro-benzenesulphonamide.

EXAMPLE 84 Analogously to Example 70(a), starting from 10.6 g. ofcyanogen bromide, the followi g en pr duct is obtained i i (a) With 27.0g. of N-(1-methyl-2-propylamino-ethyl)- p-toluenesulphonamide, M.P.91-92", l-(p-tolylsulphonyl)-2-imino 3 propyl 5 methyl imidazolidine,B.P. 183189/0.0l torr.

(b) The starting material for (a) can be produced starting fromp-toluenesulphonyl chloride, which, analogously to Example (b), isconverted with Z-methylaziridine tol-(p-tolylsulphonyl)-2-methyl-aziridine, M.P. 63-65, 21.1 g. of which,analogously to Example 70(c), with 150 ml. of propylamine yieldN-(l-methyl-Z-propylamino-ethyl)-p-toluenesulphonamide.

EXAMPLE Analogously to Example 70(a), starting from 10.6 g. of cyanogenbromide, the following end products are obtained:

(a) With 28.4 g. of N-(1-methyl-2-butylamino-ethyl)-p-toluenesulphonamide, M.P. 7375 (from ether), l-(ptolylsulphonyl 2imino 3 butyl-5-methyl-imidazolidine, B.P. l73179/0.01 torr [thestarting material is produced analogously to Example 70(0) from 21.1 g.of l-(p tolylsulphonyl) 2-methyl-aziridine and ml. of butylamine] (b)With 28.4 g. of N-(l-methyl-Z-tert. butylaminoethyl) ptoluenesulphonamide, M.P. 8283 (from ether), 1 (p-tolylsulphonyl) 2imino 3 tert. butyl- S-methyl-imidazolidine, M.P. 92-94 (from ether)[the starting material is produced analogously to Example 70(c) from21.1 g. of l-(p-tolylsulphonyl)-2-methylaziridine and 150 ml. of tert.butylamine; and

(c) With 31.0 g. ofN-(l-methyl-2-cyclohexylaminoethyl)-p-toluenesulphonamide, M.P. 58-59(from ether), 1 (p tolylsulphonyl)2-imino-3-cyclohexyl-5-methylimidazolidine, M.P. 93-94 (from ether) [thestarting material is produced analogously to Example 70(0) from 21.1 g.of l-(p-tolylsulphonyl)-2-rnethyl-aziridine and 150 ml. ofcyclohexylamine].

EXAMPLE 86 Analogously to Example 70(a), starting from 12,2 g. ofcyanogen bromide, the following end product is obtained:

(a) With 28.2 g. of N-(Z-methylamino-cyclohexyl)-ptoluenesulphonamide,M.P. 92-93 (from cyclohexane), l-(p-tolylsulphonyl)-2-imino-3methyl-hexahydro-benzimidazoline, M.P. 184-185 (from isopropanol).

(b) The starting material for (a) can be produced as follows: Startingfrom p-toluenesulphonyl chloride, it is reacted, analogously to Example70(b), with 7-azabicyclo[4.l.0]heptane [cf. 0. E. Paris et al., J. Am.Chem. Soc., 74, 3007 (1952)] to give 7-(p-tolylsulphonyl)-7-azabicyclo[4.1.0]heptane, M.P. 59-61" (from cyclohexane) analogously toExample 70(c), 25.1 g. of this intermediate product with 300 ml. 33%ethanolic methylamine yieldN-(2-methylamino-cycloclohexyl)-p-toluenesulphonamide.

EXAMPLE 87 Analogously to Example 70(a), starting from 12.2 g. ofcyanogen bromide, the following end products are obtained:

(a) With 32.4 g. of N-(2-butylamino-cyclohexyl)-ptoluenesulphonamide,M.P. 107-l08, l-(p-tolylsulphonyl)-2-imino-3-butyl hexahydrobenzimidazoline, M.P. 138-140 (from isopropanol) [the starting materialis produced analogously to Example 70(c) from 25.1 g. of7-(p-tolylsulphonyl)-7-azabicyclo[4.1.0]heptano and 300 ml. ofbutylamine]; and

(b) With 35.8 g. of N-(Z-benzylamino-cyclohexyl)-ptoluenesulphonamide,M.P. 118-ll9 (from cyclohexane) 1- (p-tolylsulphonyl) -2-imino-3-benzyl-hexahydrobenzimidazoline, M.P. 157-158 (from isopropanol) [thestarting material is produced analogously to Example 70(c) from 25.1 g.of 7-(p-tolylsulphonyl)-7-aza bicyclo[4.1.0]heptane and 300 ml. ofbenzylamine].

37 EXAMPLE 88 Analogously to Example 70(a), starting from 12.2 g. ofcyanogen bromide, the following end product is obtained:

(a) With 29.8 g. ofN-(1,1-dimethyl-2-butylaminoethyl)-p-toluenesulphonamide (crudeproduct), l-(ptolylsulfonyl)-2-imino-3-butyl 5,5-dimethyl imidazolidine,M.P. 7274 (from cyclohexane).

The starting material is produced as follows:

(b) 8.9 g. of 2-amino-2-methyl-l-propanol are dissolved in 150 ml. ofabsolute pyridine. The solution is cooled with Dry Ice/acetone to 10 andduring 30 minutes While stirring well 44.0 g. of p-toluene sulphonylchloride are added in portions at a reaction temperature of 10 to Thebrown solution is then stirred 4 hours longer at 0 and poured on to 550ml. of ice water. A resin precipitates which slowly crystallises. Thecrystals are removed by filtration, washed with water and dried undervacuum at 80. The resulting N-[1,1-dimethyl-Z-(p-tolylsulphonyloxy)ethyl] p-toluenesulphonamide melts at 98100 (crude product).

(c) 39.75 g. of the sulphonamide obtained according to (b) are suspendedin 150 ml. of toluene and 150 ml. of butylamine are added to thesuspension. The reaction mixture dissolves. The solution is allowed tostand for 4 hours at room temperature and then concentrated. The residueis treated with Water and concentrated ammonia, and the base whichprecipitates is extracted with ethyl acetate. The extract isconcentrated under vacuum, to leave crude N-(1,1-dimethyl-2butylaminoethyl)-ptoluenesulphonamide as residue.

EXAMPLE 89 Analogously to Example 70(a), starting from 12.2 g. ofcyanogen bromide, the following end products are obtained:

(a) With 32.4 g. ofN-(1,1-dimethyl-2-cyclohexylaminoethyl)-p-toluenesulphonamide (crudeproduct), 1- (p-tolylsulphonyl)-2-imino-3 cyclohexyl5,5-dimethylimidazolidine, M.P. 121-122" (from cyclohexane) [thestarting product is produced analogously to Example 88(c) from 39.7 g.of N-[1.,1-dimethyl-2-(p-tolylsulphonyloxy)-ethy1]-p-toluenesulphonamideand 150 ml. of cyclohexylamine]; and

(b) With 8.9 g. of N-(1-ethyl-2-allylarnino-ethyl)-ptoluenesulphonamide(crude product),l-(p-tolylsulphonyl)-2-imino-3-allyl-5-ethyl-imidazolidine, M.P. 75- 77(from benzene/cyclohexane) [the starting material is produced asfollows: Starting from 44.0 g. of p-toluenesulphonyl chloride, ityields, analogously to Example 88(b), with 8.9 g. of 2-amino-1-butanol,N-[1-ethy1-2- (p-tolylsulphonyloxy)-ethyl] p toluenesulphonamide, 39.75g. of which, analogously to Example 88(c), are reacted with 150 ml. ofallylamine].

EXAMPLE 90 A solution of 10.6 g. of cyanogen bromide in 50 ml. ofabsolute ether is added with stirring at to -5 within 30 minutes to asolution of 14.6 g. of butylamine in 100 ml. of absolute ether. Thereaction mixture is stirred for 30' minutes more and the precipitatedbutylamine-hydrobromide is removed by filtration. While cooling iscontinued, a suspension of 2.8 g. of sodium hydride in 40 ml. ofabsolute ether is added to the filtrate which contains the resultantbutylcyanamide in solution. While cooling at this temperature iscontinued, the suspension is stirred for another 30 minutes and then19.7 g. of l-(p-tolylsulphonyl)-aziridine are added to the suspendedsodium derivative of butyl cyanamide which has formed. The mixture iswarmed to room temperature and stirred for hours at this temperature. 2N hydrochloric acid is then slowly added to the reaction mixture and thetwo phases which form are separated. The acidic aqueous phase is Washedtwice with ether, purified with active charcoal, filtered and renderedalkaline with concentrated sodium hydroxide solution at 0. Theprecipitated l-(ptolylsulphonyl)-2-imino-3 butyl-imidazolidine isseparated by filtration and recrystallised from methanol; it then meltsat 91-92.

EXAM PLE 9 1 Analogously to Example 90, the following end products areobtained:

(a) From 14.6 g. of tert. butylamine in 100 ml. of ether with 10.6 g. ofcyanogen bromide, tert. butylcyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thisyields with 21.1 g. of l-(p-tolylsulphonyl)-2-methyl-aziridine,l-(p-tolylsulphonyl)-2-imino-tert. butyl 5 methyl-imidazolidine, M.P.929 4;

(b) From 14.6 g. of butylamine in 100 ml. of ether with 10.6 g. ofcyanogen bromide, butyl-cyanamide, which with 2.8 g. of sodium hydridein 40 ml. of ether is converted to the sodium derivative; this with 21.3g. of 1-(p-methoxy-phenylsulphonyl)-aziridine yields l-(p-methoxyphenylsulphonyl)-2-imino-3-butyl imidazolidine, M.P. -86;

(c) From 19.8 g. of cyclohexylamine in ml. of ether with 10.6 g. ofcyanogen bromide, cyclohexylcyanamide, which with 2.8 g. of sodiumhydride in 40 ml. of ether is converted to the sodium derivative; thiswith 21.75 g. of 1-(p-chloro-phenylsulphonyl)-aziridine yields 1 (pchloro phenylsulphonyl) 2 imino 3 cyclohexyl-imidazolidine, M.P. 108110;and

(d) From 11.8 g. of isopropylamine in 100 ml. of ether with 10.6 g. ofcyanogen bromide, isopropyl-cyanamide, which with 2.8 g. of sodiumhydride in 40 m1. of ether is converted to the sodium derivative; thiswith 18.4 g. of 1-phenylsulphonyl-aziridine yields 1- phenylsulphonyl-Z-imino-3-isopropyl-imidazolidine, M.P. 7172.

EXAMPLE 92 9.9 g. of l-butyl-aziridine [cf. A. Weissberger, HeterocyclicCompounds With Three and Four-Membered Rings, John Wiley & Sons Inc.,London (1964), p. 530] are dissolved in 50 ml. of dioxane, and 10.6 g.of cyanogen bromide in 50 ml. of dioxane are added thereto. In anexothermic reaction a solution of N-(2-bromo-ethyl)- N-butyl-cyanamideis obtained, which is poured with stirring into a solution of 17.1 g. oftoluene-sulphonamide in 60 ml. of 2 N sodium hydroxide solution. Thereaction mixture is refluxed for one hour, then concentrated to half itsvolume under vacuum, and the solution is cooled to 0. The precipitatedcrystals are separated by filtration, washed with water, dried undervacuum at 60 and recrystallised from ether. The resulting1-(p-tolylsulphonyl)-2-imino-3-butyl-imidazolidine melts at 91-92.

EXAMPLE 93 Analogously to Example 92 the following end products areobtained:

(a) From 9.9 g. of l-tert. butyl-aziridine with 10.6 g. of cyanogenbromide in dioxane, the solution of N-(2- bromo-ethyU-N-tert.butyl-cyanamide, which with 17.1 g. of p-toluenesulphonamide in 60 ml.of 2 N sodium hydroxide solution yields l-(p-tolylsulphonyl)-2-irnino-3-tert. butyl-imidazolidine, M.P. 131132 (from ethyl acetate);

'(b) From 13.5 g. of l-cyclohexyl-aziridine with 10.6 g. of cyanogenbromide in dioxane, the solution of N-(2-bromo-ethyl)-N-cyclohexyl-cyanamide, which with 17.1 g. ofp-toluenesulphonamide in 60 ml. of 2 N sodium hydroxide solution yieldsl-(p-tolylsulphonyl)-2-imino-3- cyclohexyl-imidazolidine, M.P. 118-120(from methanol);

(c) From 9.9 g. of l-butyl-aziridine with 10.6 g. of cyanogen bromide indioxane, the solution of N-(2- bromo-ethyl)-N-butyl-cyanamide, whichwith 18.7 g. of

p-methoxy-benzene-sulphonamide in 60 ml. of 2 N so-' dium hydroxidesolution yields l-(p-methoxy-phenylsul- 39 phonyl)-2 imino 3 butylimidazolidine, M.P. 85-86 (from methanol);

(d) From 9.9 g. of l-tert. butyl-aziridine with 10.6 g. of cyanogenbromide in dioxane, the solution of N-(2- bromo-ethyl)N-tert.butyl-cyanamide, which with 18.7 g. of p-methoxy-benzene-sulphonamide in60 ml. of 2 N sodium hydroxide solution yieldsl-(p-methoxy-phenylsulphonyl)-2-imino-3-tert. butyl-imidazolidine, M.P.107- 108 (from methanol);

(e) From 9.9 g. of l-butyl-aziridine with 10.6 g. of cyanogen bromide indioxane, the solution of N-(2- bromo-ethyl)-N-butyl cyanamide, whichwith 20.3 g. of p-methylthio-benzene-sulphonamide in 60 ml. of 2 Nsodium hydroxide solution yields l-(p-methylthio-phenylsulphonyl)-2-imino-3-butyl imidazolidine, M.P. 87-88 (from ether);

(f) From 9.9 g. of l-tert. butyl-aziridine with 10.6 g. of cyanogenbromide in dioxane, the solution of N-(Z- bromo-ethyl)N-tert.butyl-cyanamide, which with 20.3 g. of p-methylthiobenz/enesulphonamidein 60 ml. of 2 N sodium hydroxide solution yieldsl-(p-methylthio-phenylsulphonyl)-2-imino-3-tert. butyl-imidazolidine,M.P. 138- 139" (from ethyl acetate);

(g) From 12.5 g. of l-cyclohexyl-aziridine with 10.6 g. of cyanogenbromide in dioxane, the solution of N-(Z-bromo-ethyl)-N-cyclohexyl-cyanamide, which with 20.3 g. ofp-methylthiobenzenesulphonamide in 60 ml. of 2 N sodium hydroxidesolution yieldsl-(p-methylthio-phenylsulphonyl)-2-imino-3-cyclohexyl-imidazolidine,M.P. 129- 130 (from ethyl acetate);

(h) From 8.5 g. of l-propyl-aziridine with 10.6 g. of cyanogen bromidein dioxane, the solution of N-(2- bromo-ethyl)-N-propyl-cyanamide, whichwith 19.1 g. of p-chloro-benzenesulphonamide in 60 ml. of 2 N sodiumhydroxide solution yields 1-(p-chloro-phenylsulphonyl)-2-imino-3-propyl-imidazolidine, M.P. 68-69;

(i) From 9.9 g. of l-butyl-aziridine with 10.6 g. of cyanogen bromide indioxane, the solution of N-(2- bromo-ethyl)-N-butyl-cyanamide, whichwith 19.1 g. of p-chloro-benzene-sulphonamide in 60 ml. of 2 N sodiumhydroxide solution yields l-(p-chloro-phenylsulphonyl)-2-imino-3-butyl-imidaz0lidine, M.P. 74-75 (from ether);

(j) From 12.5 g. of l-cyclohexyl-aziridine with 10.6 g. of cyanogenbromide in dioxane, the solution of N-(2-bromo-ethyl)-N-cyclohexyl-cyanamide, which with 19.1 g. ofp-chloro-benzene-sulphonamide in 60 ml. of 2 N sodium hydroxide solutionyields l-(p-chlorophenylsulphonyl)-2-imino-3-cyclohexyl-imidazolidine,M.P. 108- 110 (from ethyl acetate/ ether);

(It) From 8.5 g. of l-isopropyl-aziridine with 10.6 g. of cyanogenbromide in dioxane, the solution of N-(2-bromo-ethyl)-N-isopropyl-cyanamide, which with 15.7 g. ofbenzenesulphonamide in 60 ml. of 2 N sodium hydroxide solution yields1-phenyl-sulphonyl-2-imino-3-isopropyl-imidazolidine, M.P. 71-72 (fromethyl acetate/ ether); and

(1) From 12.5 g. of l-cyclohexyl-aziridine with 10.6 g. of cyanogenbromide in dioxane, the solution of N-(2-bromo-ethyl)-N-cyclohexyl-cyanamide, which with 15.7 g. ofbenzenesulphonamide in 60 ml. of 2 N sodium hydroxide solution yields1-phenyl-sulphonyl-2-imino-3-cyclohexyl-imidazolidine, M.P. 94-95" (fromethyl acetate).

EXAMPLE 94 (a) 30.3 g. ofN-(2-brorno-ethyl)-N-cyano-p-toluenesulphonamide are dissolved in 500ml. of ethanol and 7.3 g. of tert. butylamine, and refluxed for 17hours. The reaction mixture is concentrated and the residue is taken upin chloroform and 2 N hydrochloric acid. The acidic aqueous extract isrendered alkaline with concentrated sodium hydroxide solution. The crudeproduct precipitates; it is filtered and purified by recrystallisationfrom ethyl acetate. The resulting l-(p-tolylsulphonyl)-2-imino-3-tert.butyl-imidazolidine melts at 13013l.

The starting material is produced as follows:

(b) During minutes a solution of 4.3 g. of aziridine in 20 ml. of etheris added dropwise at 0 to a solution of 10.6 g. of cyanogen bromide in30 ml. of ether. The resulting suspension is concentrated under vacuumat a bath temperature of The residue is slurried in ml. of water and asolution of 19.9 g. of p-toluenesulphonyl chloride in 190 ml. of acetoneis added to the suspension. 4.5 g. of sodium hydroxide in 10 ml. ofwater are then added dropwise during 10 minutes and the resultingmixture is refluxed for 30 minutes. After cooling, the crude productcrystallises. It is filtered. Upon dilution with water, the filtrateyields another batch of crude product, which is separated and combinedwith the first fraction. The two fractions are recrystallised frommethanol to yield N- (2-bromo-ethyl) -N-cyano-p-toluenesulphonamidemelting at 67-69".

EXAMPLE Analogously to Example 94, starting from 30.3 g. of N (2bromo-ethyl)-N-cyano-p-toluenesulphonamide in 500 ml. of ethanol, thefollowing are obtained:

(a) With 5.9 g. of propylamine, l-(p-tolylsulphonyD-Z-imino-3-propyl-imidazolidine, M.P. 95-96; and

(b) With 9.9 g. of cyclohexylamine, l-(p-tolylsulphonyl) 2imino-3-cyclohexyl-imidazolidine, M.P. l18-120 (from methanol).

EXAMPLE 96 (a) 36.0 g. ofN-(N'-benzyl-2-butylamino-ethyl)-ptoluenesulphonamide are dissolved in500 ml. of benzene. 10.6 g. of cyanogen bromide are added to thesolution, the reaction mixture is stirred for 3 hours at roomtemperature and then concentrated. The residue is rendered alkaline with2 N sodium hydroxide solution. Crystals precipitate, which are washedwith water and recrystallised from methanol/ether. The resulting, purel-(p-tolylsulphonyl) 2 imino-3-butyl-imidazolidine melts at 9l-92 (fromether).

The starting material is produced as follows:

(b) 24.0 g. of l-(p-tolylsulphonyl)-aziridine are dissolved in ml. ofdioxane and 20 ml. of water, and refluxed for 5 hours with stirring. Thereaction mixture is then concentrated. The residue,N-(N-benzyl-2-butylamino-ethyl)-p-toluenesulphonamide, is used as crudeproduct.

EXAMPLE 97 (a) 33.15 g. of the addition salt of p-tolylsulphonylcyanamide and N-(2-chloro-ethyl)-tert. butylamine are heated for onehour at a bath temperature of 145. The melt is cooled and trituratedwith 2 N hydrochloric acid. The solution is decanted to remove insolubleresin and rendered alkaline with concentrated sodium hydroxide solution.The precipitated l-(p-tolylsulphonyl)-2-imino-3- tert.butyl-imidazolidine is filtered, rinsed with water and recrystallisedfrom ethyl acetate; it then melts at -131 The starting material isproduced as follows:

(b) 19.0 g. of p-toluenesulphonyl chloride and 50 ml. of dioxane areadded with stirring to a solution of 8.6 g. of disodium cyanamide in 100ml. of water. An exothermic reaction takes place and thep-toluenesulphonyl chloride dissolves. The solution is stirred for 15minutes and then a solution of 17.2 g. of N(2-chloro-ethyl)-tert.butylamine-hydrochloride in 40 ml. of water is added. The reac tionmixture is allowed to stand at room temperature for 2 hours; it is thenconcentrated to half its volume. The oil which precipitates is extractedwith methylene chloride, the organic phase is separated, dried oversodium sulphate and concentrated. The residue, the addition salt ofp-toluenesulphonyl cyanamide and N (2 chloro-ethyl)-tert. butylamine, isrecrystallised from isopropanol; it then melts at 103-104.

EXAMPLE 98 17.8 g. of 1-butyl-2-imino-imidazolidine-hydrochloride aredissolved in 100 ml. of water and 6.0 g. of sodium

